Confirming Diagnosis of Hepatitis C Infection: The initial hepatitis C evaluation may involve a person newly diagnosed with hepatitis C infection, or an individual previously diagnosed with hepatitis C who is establishing or reestablishing clinical care for their hepatitis C infection. First, the clinician should review the hepatitis C test results and confirm the patient has chronic hepatitis C virus (HCV) infection and not resolved HCV.
General Approach to Initial Evaluation: During the initial evaluation, the clinician should perform a thorough history and physical examination, focusing particularly on risk factors for acquiring HCV infection, presence of significant medical comorbidities, psychiatric history, coinfection with other viruses, stigmata of chronic liver disease, clinical manifestations attributable to hepatitis C infection, prior assessment of liver fibrosis, and a history of prior treatment. In addition, the initial evaluation should assess for any ongoing risk of HCV transmission, ascertain for use of alcohol or any other substance that would cause further liver toxicity, and identify barriers to treatment. Assessment of the stage of liver disease is a complex task and should be addressed in subsequent follow-up visits.
Identifying Risk Factors for HCV Acquisition: Identifying an individual patient’s risk factor for HCV acquisition is important in order to properly counsel the patient regarding risk of onward transmission and prevention of re-infection. In the United States, the major risk factors for HCV acquisition are injection drug use (IDU), receipt of a blood transfusion or organ transplant prior to 1992, exposure to an infected sexual partner, occupational needlestick injury, tattooing, and mother-to-child transmission. Recently, there has been recognition of a sexually transmitted hepatitis C epidemic among men who have sex with men (MSM), particularly men with HIV infection. Some individuals may not disclose a possible risk factor for acquiring hepatitis C at the initial visit and when this occurs the clinician should readdress this issue at a later point after they have hopefully established a good rapport with the patient. The reluctance to disclose risk of HCV acquisition is particularly common in individuals who have a remote history of injection drug use.
Alcohol History: Determining the presence of current and prior alcohol is important for two major reasons. First, the ongoing alcohol intake of even moderate amounts (50 g/day or more) leads to ongoing hepatotoxicity and accelerated progression of liver fibrosis. Second, even in the interferon-free era, ongoing heavy alcohol use can be a major barrier to treatment of HCV. Because denial is often intertwined with chronic ethanol use, obtaining an accurate history can be difficult. Several well-validated tools are recommended for alcohol abuse screening, including the CAGE Questionnaire, a 4-question screening tool (Figure 1), and the Alcohol Use Disorders Identification Test (AUDIT). The AUDIT-C is a 3-question modified version of the 10-question AUDIT screening instrument and a more practical tool than the AUDIT in clinical settings (Figure 2). No consensus opinion exists regarding treatment of individuals with a history of alcohol abuse who have ongoing infrequent alcohol consumption, but many HCV-treating clinics use a minimum criterion of 6 months of sobriety as a general measure of readiness for therapy.
Injection Drug Use History: For patients with a history of past or present injection-drug use, it is important to assess whether they have active drug use or are likely to use again in the future. Asking about injection-drug use may aid in determining the initial mode of infection, which informs further screening for co-infections, such as HIV and hepatitis B virus. In addition, it is also helpful to determine the age of first drug use, since this may give insight into the likely duration of HCV infection, which in turn may provide indirect evidence for severity of liver disease. Individuals with active injection-drug use should receive counseling on safe injection practices to prevent onward transmission of HCV, and should be offered appropriate treatment and support towards abstinence. Ongoing active injection-drug use is not an absolute contraindication to treatment of hepatitis C, but it can impact the complex decision to treat, mainly due to potential difficulty in adhering to treatment and risk for re-infection with HCV.
Psychiatric History: Patients with HCV infection have a higher incidence of psychiatric illness compared with the general population, and comorbid, inadequately treated psychiatric illness represented a major barrier to successful HCV treatment in ther interferon era. Interferon-based therapies for HCV have important neuropsychiatric side effects, such as depression, irritability, mood swings, and suicidality. New direct acting antivirals do cause neuropsychiatric adverse effects. In the modern treatment era, psychiatric issues take on less importance, but may still be a barrier to care with regard to linkage to care, adherence, and substance abuse.
Presence of Medical Comorbidities: When evaluating the patient with hepatitis C infection, the clinician should consider secondary causes of liver disease, such as non-alcoholic fatty liver disease (NAFLD), alcoholic hepatitis, or autoimmune hepatitis. Obesity and insulin resistance have been associated with inferior hepatitis C treatment responses. Guidelines advise the clinician to counsel those who are overweight (defined as Body Mass Index [BMI] greater than 25 kg/m2) to attempt to lose weight prior to initiating treatment. The calculation of the patient’s BMI is based on the patient’s weight (pounds) and height (inches) (Figure 3). The National Heart, Lung, and Blood Institute has an on-line BMI Calculator and BMI Tables for interpreting the calculated result. Congestive heart failure, anemia, psychiatric disease, renal insufficiency, thyroid disease, or autoimmune conditions are relative contraindications to receiving interferon-based therapy for HCV and thus are important to identify. Ribavirin is absolutely contraindicated in pregnant women and their male partners.
Presence of Significant Coinfections: Every newly diagnosed patient should undergo screening for a history of hepatitis A virus (HAV), hepatitis B virus (HBV), and human immunodeficiency virus (HIV). Coinfection with either HBV or HIV is known to accelerate the rate of hepatic fibrosis, and acute HAV in a patient with HCV can lead to fulminant hepatic failure. In the absence of immunity to HAV and HBV, immunization should be offered.
Prior Staging of Liver Fibrosis: For persons previously engaged in clinical care for their hepatitis C infection, it is important to determine whether they have had a liver biopsy. If so, the date of the biopsy, sample size, and fibrosis scoring system, and fibrosis score should be recorded in the medical record. In addition, the clinician should note any prior evaluation for liver fibrosis using a non-invasive method, such as hepatic ultrasound, transient elastography, serum-based Aspartate aminotransferase-to-Platelet Ratio Index (APRI), and FibroTest.
Complications of Liver Disease: Upon initial evaluation, it is important to determine whether the patient has already experienced complications of advanced liver disease. Treatment of HCV in cirrhotic patients is complex, and may require referral or consultation with a provider who has expertise in hepatology. The clinician should inquire about prior hospital admissions for ascites, hepatic encephalopathy, jaundice, or gastrointestinal bleeding. Furthermore, untreated hepatocellular carcinoma or the presence of decompensated cirrhosis (Child-Turcotte-Pugh class C, typically with ascites, encephalopathy, coagulopathy, or hyperbilirubinemia) indicates a need for prompt referral to a hepatologist.
Extrahepatic Clinical Manifestations Attributable to Hepatitis C Infection: Hepatitis C infection may be associated with a diverse array of extrahepatic manifestations, such as arthralgias, neuropathy, nephropathy, glomerulonephritis, livedo reticularis, lichen planus, and cold agglutinin disease. As part of the initial evaluation, the clinician should inquire about any known extrahepatic complications. In one large study, the most common symptoms in patients who had extrahepatic manifestations were arthralgia (23%), paresthesia (17%), myalgia (15%), pruritus (15%), and sicca syndrome (11%).
History of Prior Treatment for Hepatitis C: For individuals who have previously undergone unsuccessful treatment for HCV the clinician must determine the type, timing and duration of prior treatment, degree of adherence, adverse effects, and if possible, viral kinetics and outcome on treatment. Failure to achieve a sustained virologic response (SVR) occurs as a result of non-response or relapse. Non-Responders are patients who never cleared HCV from their serum during the course of treatment. Among the Non-Responders, those classified as Null Responders failed to achieve a 2-log reduction in HCV viral load after 12 weeks of therapy whereas Partial Responders are those who achieved a greater than 2-log decrease in HCV viral load at week 12 of therapy, but the HCV RNA level remained detectable at week 24 (Figure 4). Relapsers have virologic rebound after achieving an end-of-treatment response, with this usually occurring within the first 24 weeks after treatment completion (Figure 5).