Acute Hepatitis C and other Causes of Acute Viral Hepatitis - pharmacyteach

 ACUTE HEPATITIS C & OTHER CAUSES OF ACUTE VIRAL HEPATITIS

 

Overveiw 

In addition to HAV and HBV, other viruses that can lead to hepatitis include the hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV), the latter being an enterically transmitted form of hepatitis that is prevalent in epidemic outbreaks across Asia, the Middle East, and North Africa. The hepatitis G virus (HGV) is rarely associated with significant hepatitis. Furthermore, a DNA virus known as the TT virus (TTV) has been detected in up to 7.5% of blood donors and is easily transmitted through blood transfusions; however, a direct link between this virus and liver disease has not been confirmed. Additionally, a related virus called SEN-V has been identified in 2% of blood donors in the United States, is also transmitted via transfusion, and may contribute to certain instances of transfusion-related non-ABCDE hepatitis. In individuals with compromised immune systems, as well as in some rare cases of immunocompetent individuals, cytomegalovirus, Epstein-Barr virus, and herpes simplex virus should be included in the differential diagnosis for hepatitis. Moreover, severe acute respiratory syndrome (SARS) and influenza have been noted to cause significant elevations in serum aminotransferases. A small fraction of acute viral hepatitis cases remain attributed to unidentified pathogens.

1. Hepatitis C

HCV, a single-stranded RNA virus classified as a hepacivirus, shares similarities with flaviviruses. Researchers have identified seven main genotypes of HCV. In earlier times, HCV was implicated in over 90% of post-transfusion hepatitis cases, yet only 4% of hepatitis C cases were due to blood transfusions. More than half of the infections are linked to injection drug use, with both reinfection and superinfection being common among individuals who inject drugs. Additional risk factors include body piercing, tattoos, and hemodialysis. The risk of transmission through sexual contact and from mother to neonate is low, although it may be higher in certain patients with significant levels of HCV RNA. Having multiple sexual partners can elevate the risk of HCV infection, and factors such as co-infection with HIV, unprotected receptive anal intercourse with ejaculation, and methamphetamine use during sex can further increase the risk of HCV transmission among men who have sex with men. Transmission through breastfeeding has not been observed.

A hepatitis C outbreak has been reported among patients with immune deficiencies, particularly in those who received intravenous immune globulin. Transmission has occurred in both hospital and outpatient settings through the use of multidose saline vials for flushing Portacaths, the reuse of disposable syringes (including instances of drug diversion by infected healthcare personnel), contamination of shared saline, radio-pharmaceutical, and sclerosant vials, inadequately sterilized endoscopy equipment, and between patients in liver units. In developing countries, unsafe medical practices contribute significantly to the incidence of HCV infections. Reports indicate covert transmission during violent altercations, with incarceration being a contributing risk factor, observed at a rate of 26% in the United States. The origin of infection remains unidentified in many patients. Coinfection with HCV occurs in at least 30% of individuals infected with HIV. The presence of HIV significantly heightens the risk of acute liver failure and accelerates the progression of chronic hepatitis C to cirrhosis; furthermore, HCV exacerbates the hepatotoxic effects of highly active antiretroviral therapy. The prevalence of chronic HCV infections in the United States has declined from 3.2 million in 2001 to 2.3 million in 2013. Although the incidence of new cases of acute, symptomatic hepatitis C decreased from 1992 to 2005, a rise was noted among individuals aged 15 to 24 between 2002 and 2006, attributed to injection drug use.

 

Clinical Findings

 

A. Symptoms and Signs

 The average incubation period for hepatitis C is between 6 to 7 weeks, with clinical manifestations typically being mild and often asymptomatic. This condition is marked by fluctuating elevations in aminotransferase levels and a significant prevalence (over 80%) of chronic hepatitis. Spontaneous resolution of HCV after acute infection occurs more frequently (64%) in individuals possessing the CC genotype of the IL28B gene compared to those with the CT or TT genotypes (24% and 6%, respectively). Individuals with the CC genotype are also more prone to develop jaundice during acute hepatitis C. Furthermore, patients with chronic hepatitis C and the CC genotype are more likely to respond favorably to treatment with Pegylated interferon (refer to Chronic Viral Hepatitis). In pregnant women diagnosed with chronic hepatitis C, serum aminotransferase levels often return to normal despite ongoing viremia, only to rise again post-delivery.

B. Laboratory Findings

Hepatitis C diagnosis is conducted through an enzyme immunoassay (EIA) that detects antibodies against HCV. The presence of anti-HCV does not confer immunity, and in patients suffering from acute or chronic hepatitis, its detection in serum usually indicates that HCV is the causative agent. The EIA has certain drawbacks, such as moderate sensitivity that may result in false negatives during the early phase of acute hepatitis C, and low specificity that can lead to false positives in some individuals with high gamma-globulin levels. In these instances, confirmation of hepatitis C can be achieved by testing for HCV RNA. It is also noted that some individuals may have anti-HCV in their serum without the presence of HCV RNA, which suggests they have recovered from a past HCV infection.

 

Complications

HCV is a pathogenic factor in the development of mixed cryoglobulinemia and membranoproliferative glomerulonephritis, and it may also be linked to lichen planus, autoimmune thyroiditis, lymphocytic sialadenitis, idiopathic pulmonary fibrosis, sporadic porphyria cutanea tarda, and monoclonal gammopathies. The infection with HCV increases the risk of non-Hodgkin lymphoma by 20-30%. Hepatic steatosis is particularly associated with HCV genotype 3, although it may also be present in patients infected with other HCV genotypes who have risk factors for fatty liver. On the other hand, chronic HCV infection is associated with a decrease in serum cholesterol and low-density lipoprotein levels.

 

Prevention

Testing for HCV in donated blood has effectively reduced the risk of transfusion-related hepatitis C from 10% in 1990 to roughly 1 case per 2 million units by 2011. The CDC and the US Preventive Services Task Force have recommended that individuals born between 1945 and 1965, known as 'baby boomers', undergo screening for HCV infection, which could potentially identify over 900,000 new cases. Those infected with HCV should adhere to safe sex practices; however, there is minimal evidence that HCV is readily transmitted through sexual contact or during childbirth, and no specific preventive measures are advised for individuals in monogamous relationships or for pregnant women. Vaccination against HAV (following prescreening for prior immunity) and HBV is advised for patients with chronic hepatitis C, and vaccination against HAV is also recommended for those with chronic hepatitis B.

Treatment

Treating patients with acute hepatitis C using peginterferon for duration of 6 to 24 weeks significantly lowers the risk of developing chronic hepatitis. Generally, individuals infected with HCV genotype 1 require a treatment course of 24 weeks; however, a 12-week course may be adequate if HCV RNA is undetectable in the serum by the fourth week. Those with genotypes 2, 3, or 4 typically need 8 to 12 weeks of therapy. Notably, about 20% of patients with acute hepatitis C, especially those who are symptomatic, may clear the virus without treatment, suggesting that it may be wise to reserve treatment for patients whose serum HCV RNA levels do not clear after three months. If HCV RNA does not clear after three months of peginterferon, ribavirin may be added, although some experts recommend using ribavirin in conjunction with peginterferon from the start of treatment. The advent of new oral direct-acting agents is likely to replace interferon-based therapies (see Chronic Viral Hepatitis).

Prognosis

In most patients, clinical recovery is complete in 3-6 months. Laboratory evidence of liver dysfunction may persist for a longer period. The overall mortality rate is less than 1%. but the rate is reportedly higher in older people. Fulminant hepatitis C is rare in the United States.

Chronic hepatitis, which typically progresses slowly, affects nearly 85% of individuals with acute hepatitis C. Ultimately, cirrhosis may develop in as many as 30% of those with chronic hepatitis C; the risk of cirrhosis and hepatic decompensation is heightened in patients who are coinfected with both HCV and HBV or HIV. Those with cirrhosis are at an annual risk of 3.5% for developing hepatocellular carcinoma. Long-term morbidity and mortality rates in chronic hepatitis C patients are lower among black individuals compared to white individuals, with the lowest rates found in those with HCV genotype 2 and the highest in those with HCV genotype 3.

 

2. Hepatitis D (Delta Agent)

HDV is a defective RNA virus that causes hepatitis only in association with HBV infection and specifically only in the presence of HBsAg: it is cleared when the latter is cleared.

 

The hepatitis D virus (HDV) may co-infect individuals already infected with hepatitis B virus (HBV) or may superinfect those with chronic hepatitis B, usually through percutaneous routes. When acute hepatitis D coincides with acute HBV infection, the severity of the condition is typically similar to that of acute hepatitis B by itself. In chronic hepatitis B cases, superinfection with HDV is associated with a poorer short-term prognosis, often resulting in fulminant hepatitis or severe chronic hepatitis that advances quickly to cirrhosis.

In the United States, new cases of hepatitis D are now rare, mainly due to the successful control of HBV infections. The cases that do occur are generally among individuals, who were infected long ago, managed to survive the initial effects of hepatitis D, and currently suffer from cirrhosis. Such patients are at an elevated risk for decompensation and have a threefold higher chance of hepatocellular carcinoma. Most new cases are found in immigrants from areas where the disease is prevalent, including Africa, Central Asia, Eastern Europe, and Brazil's Amazon region.

More than 15 million people are infected worldwide. The diagnosis of hepatitis D is made by detection of antibody to hepatitis D antigen (anti-HDV) and, where available, hepatitis D antigen (HD Ag) or HDV RNA in serum.

 

3. Hepatitis E

HEV, a hepevirus of 29 to 32 nanometers in size from the Hepeviridae family, is a primary cause of acute hepatitis in regions such as Central and Southeast Asia, the Middle East, and North Africa, where it is responsible for outbreaks of waterborne hepatitis. While it is infrequent in the United States, it should be taken into account for patients with acute hepatitis who have traveled to endemic areas. In industrialized nations, it may be transmitted through swine, and having pets at home and consuming undercooked organ meats are considered risk factors. The disease is generally self-limiting without a carrier state; however, cases of chronic hepatitis with rapid progression to cirrhosis due to HEV have been documented in transplant recipients, particularly when tacrolimus is used as the main immunosuppressant, and, on rare occasions, in individuals with HIV, preexisting liver disease, or those receiving chemotherapy for cancer.

The diagnosis of acute hepatitis E is primarily established through the detection of IgM anti-HEV antibodies in serum, although the reliability of existing tests may be questionable. Extra hepatic manifestations reported include arthritis, pancreatitis, monoclonal gammopathy, thrombocytopenia, and various neurological complications such as Guillain-Barre syndrome and peripheral neuropathy. In regions where the disease is endemic, the mortality rate among pregnant women is notably high (10-20%) and is associated with elevated levels of HEV RNA in serum and genetic mutations that result in diminished expression of progesterone receptors. Additionally, patients with pre-existing chronic liver disease face an increased risk of hepatic decompensation. A treatment regimen of oral ribavirin over three months has been shown to achieve sustained clearance of HEV RNA from serum in 78% of patients. Enhancing public hygiene practices can mitigate the risk of HEV infection in endemic regions. Furthermore, recombinant vaccines targeting HEV have demonstrated potential in clinical trials.

References:

 

1.     Kabiri M et al. The changing burden of hepatitis C virus infec-tion in the United States: model-based predictions. Ann Intern Med. 2014 Aug 5;161(3):170-80. [PMID: 25089861]

2.     Kamar N et al. Ribavirin for chronic hepatitis E virus infection in transplant recipients. N Engl J Med. 2014 Mar 20;370(12): 1111-20. [PMID: 24645943]

3.     Lo Re V 3rd et al. Hepatic decompensation in antiretroviral-treated patients co-infected with HIV and hepatitis C virus compared with hepatitis C virus-monoinfected patients: a cohort study. Ann Intern Med. 2014 Mar 18;160(6):369-79. [PMID: 24723077]