Chronic hepatitis: Epidemiology, clinical features, and management

Epidemiology

Hepatitis C virus (HCV) is an RNA virus and a member of the family Flaviviridae. This disease affects approximately 1.6% of the American population, with estimates at three to four million infected. Most commonly, the disease is transmitted by blood-to-blood contact. Before the availability of the hepatitis C antibody test in the early 1990s, posttransfusion hepatitis C was a common means of transmission. However, the availability of reliable assays has led to a marked decrease in the incidence of posttransfusion hepatitis C. Currently, the risk of posttransfusion hepatitis C is approximately 1 in 2 million transfusions. The much more common risk factor for contracting hepatitis C is intravenous drug use. Other needle-stick exposures, such as tattoos and occupational exposure, account for a much lower percentage of cases. Sexual transmission is likewise a low risk, particularly among monogamous partners. However, the prevalence of hepatitis C is much higher at sexually transmitted disease clinics, affecting nearly 10% of nonintravenous drug-using patients seen at such clinics, presumably related to sexual promiscuity and traumatic sex, with increased risk of blood-borne exposure. Vertical transmission occurs in 4% to 6% of children of hepatitis C viremic mothers, with the incidence increasing to 10% to 11% of children of mothers with human immunodeficiency virus (HIV)/HCV co-infection. Inhalation of cocaine has been raised as a potential risk factor, based on the transmission via blood on straws used to snort the inhaled agent. This risk factor has been questioned, with the issue that inhaled cocaine may be associated with other high-risk behavior that is, in fact, the mode of transmission.

Presentation

Patients with chronic hepatitis C are frequently asymptomatic, although many have nonspecific symptoms, usually related to fatigue, myalgias, arthralgias, and/or right upper quadrant discomfort. Most patients are only diagnosed when they seek medical care for other reasons or have the symptoms just mentioned and are found to have mild elevations of the transaminases. However, as many as 30% of patients will have normal transaminases at any one time, as the transaminases may wax and wane with time. Thus a history of any of the risk factors outlined earlier should lead to serologic testing to rule out hepatitis C. Due to the absence of risks factors in some patients, the Centers for Disease Control and Prevention (CDC) recommended one time screening with a hepatitis C antibody in those born from 1945 to 1965.

Diagnosis

The standard screening study for hepatitis C is an enzyme-linked immunosorbent assay (ELISA) for antibody to hepatitis C. This is the standard test used by blood banks around the country and has a sensitivity and specificity in high-risk populations ranging from 98% to 100%. If a patient has a known risk factor and elevated transaminases, a positive hepatitis C antibody study by ELISA is consistent with the diagnosis of hepatitis C. The presence of hepatitis viremia is confirmed with a reverse transcriptase polymerase chain reaction (PCR). Unfortunately, the PCR may take days to a week to get results, depending on the frequency of testing at the local laboratory. Patients can have a positive antibody study without viremia, if the acute infection spontaneously resolved, an event that occurs 15% to 40% of the time. Antibody positivity frequently persists indefinitely, but does not imply infection if viremia is absent, based on an undetectable viral load by PCR. Patients will have one of six genotypes, which are variants in the hepatitis C genome that mainly reflect responsiveness to antiviral therapy. A genotype need not be checked if only screening a patient before surgery. However, if antiviral therapy is considered, a genotype will provide important information regarding the chance of a virologic response and the length of therapy. Genotype 1 is the most common genotype in the United States, accounting for 70% of cases. Genotype 2 accounts for 15% of cases and genotype 3 for another 10% of cases. Genotype 4 is occasionally seen in the United States, although it is more commonly seen in the Middle East and northern and central Africa. Genotypes 5 and 6 are seen in the United States, although rarely, with a higher prevalence in South Africa and Southeast Asia, respectively.

Natural history

The course of hepatitis C is quite variable and can be influenced by a number of factors. Progression of the disease is routinely measured by decades. One commonly quoted figure is that 20% of those with the disease for at least 20 years will have cirrhosis (see Chapter 74 ). It is important to keep in mind that this implies that 80% of those with the disease for 20 years do not have cirrhosis. Another important consideration in determining the extent of the disease at the time of surgical evaluation is knowledge of when the disease was contracted. For example, if the patient knows they received a blood transfusion at the time of a motor vehicle accident 35 years ago, they have probably had the disease for 35 years. Likewise, a patient with an extensive history of intravenous drug use as a young adult has likely had the disease for several decades, if currently in the sixth or seventh decade of life. The disease takes an accelerated course in patients with excessive alcohol use, contraction of the disease at a later age, and co-infection with HIV or the hepatitis B virus. ^,

Treatment

Hepatitis C treatment was previously centered around the use of pegylated interferon (PEG IFN) and ribavirin. This treatment was poorly tolerated, associated with a 45% to 50% response rate for genotype 1 patients, and lasted for 24 to 48 weeks. The addition of a protease inhibitor markedly improved response rates; however, significant side effects were seen, often leading to dose reduction, treatment cessation, or hospitalization.

In the fall of 2014, two new regimens were added to the available treatments. Sofosbuvir was combined with ledipasvir, an NS5a inhibitor, in a single-pill regimen for patients with genotype 1. Following 12 weeks of therapy, sustained virological response (SVR) rates of 95% were seen with 12 weeks of therapy. Patients with cirrhosis required 24 weeks of therapy, although with similar rates of response. Currently, five different oral agents are commonly used: sofosbuvir/ledipasvir (genotypes 1 and 4), elbasvir/grazoprevir (genotypes 1 and 4), sofosbuvir/velpatasvir (all genotypes), glecaprevir/pibrentasvir (all genotypes), and sofosbuvir/velpatasvir/voxilaprevir (all genotypes with previous non-response to agents listed). Treatment routinely lasts from 8 to 12 weeks, depending on the agent, with response rates in the range of 95% and higher. Side effects tend to be mild, with rare need to discontinue treatment.

Drug–drug interactions can either increase or decrease drug levels; thus, careful attention to the list of other medications is crucial to safely treating chronic hepatitis C. ^,

If undetectable viremia is achieved during therapy, a viral load is routinely checked 3 months following the end of therapy. An undetectable viral load at that point is consistent with an SVR or “cure.” Long-term studies have shown this response is durable, with undetectable viral loads persisting indefinitely, unless the patient is reinfected due to reexposure through intravenous drug use or high-risk sexual contact. Patients who do not respond to antiviral therapy may benefit from a treatment trial with a different agent.

Surgery in the patient with hepatitis C

In the noncirrhotic patient with hepatitis C undergoing hepatopancreatobiliary surgery, no special precaution need be taken. The risk of decompensation postoperatively is solely associated with the presence of advanced fibrosis and is not associated with the presence of the HCV itself (see Chapters 74 and 101 ) If a patient happens to be on antiviral therapy at the time of surgery, the best action is to ask a hepatologist to assess the situation. In most cases, antiviral therapy need not be stopped in the face of surgery. Antiviral therapy can be stopped if more pressing issues are at hand. Stopping antiviral therapy for a period of weeks may necessitate restarting treatment.

Epidemiology

Hepatitis B virus is a DNA virus representing the number one cause of chronic viral hepatitis worldwide, with more than 2 billion people infected at some point and more than 350 million infected chronically. More than 45% of the world’s population lives in endemic areas, particularly in Asia and sub-Saharan Africa. More than 8% of the population in these areas is positive for hepatitis B surface antigen (HBsAg). The prevalence is much lower on the North American continent, affecting less than 2% of the population overall. In the United States, approximately 73,000 new cases occur each year, with approximately 1.25 million patients infected chronically. However, due to the mobility of the world’s population, the possibility of acute or chronic hepatitis B must be considered in patients who have come to the United States from endemic areas, for professional, educational, and/or personal reasons. Changes in patterns of immigration will likely increase the prevalence of the disease by as much as a factor of two.