NATAP REPORTS

Current Review & Update on Hepatitis C & HIV/HCV Cection

SUUMER 2001

Assessment of disease severity

In HIV-infected individuals, quantitation of the amount of HIV-1 RNA in plasma is both an important predictor of disease progression and a measurement of the efficacy of antiretroviral therapy. Additionally, the peripheral blood CD4+ T cell count provides important information concerning the severity of the disease. In HCV, several indicators can be used to assess the degree of disease severity: biochemical measurements (serum quantitation of alanine aminotransferase, ALT), virologic measurements (measurement of HCV RNA), and histologic measurements (degree of fibrosis and inflammation on liver biopsy). Unfortunately, symptoms do not usually present in chronic HCV infection until the development of end stage liver disease. These symptoms (ascites, encephalopathy, prolonged prothrombin time, elevated bilirubin, decreased serum albumin) comprise the Childs-Pugh scoring system, the most frequently used measure to assess damage in end stage liver disease.

Role of Liver Biopsy in Hepatitis C

The liver biopsy is the most specific test for the diagnosis and assessment of hepatic pathology. The first liver biopsy was performed in 1883 and the technique became widely used as a diagnostic method for liver disease in the late-1950s. Liver biopsies can be performed through the abdominal wall (percutaneous), through the jugular vein (transjugular), or through a laparoscope (laparoscopic liver biopsy).

The biopsy specimen represents 1/50,000 of the total mass of the liver, which is usually sufficient for the assessment of diffuse hepatic disease. In the management of chronic hepatitis C, the assessment of hepatic pathology can provide important information regarding the prognosis and management of the infection. In HCV, the amount of hepatic fibrosis, as opposed to the level of HCV RNA, is the most important prognostic factor.

Currently, the only method by which to quantitate the amount of hepatic fibrosis is through a liver biopsy, which should be performed in any HCV-infected individual being considered for treatment. The biopsy is graded for the amount of inflammation and the stage of fibrosis on a 0 to 4 scale. Treatment should be more aggressively pursued in a patient who has stage 2-3+ fibrosis in the liver. Additionally, there is a poor correlation between the aminotransferase level (ALT) and hepatic histological features that may result from HCV. A subgroup of HCV infected individuals may have normal aminotransferase levels with clinically significant fibrosis or cirrhosis. Therefore, most hepatologists recommend a liver biopsy for histologic assessment of the liver regardless of the aminotransferase or HCV RNA levels.

Although very rare, intraperitoneal hemorrhage is the most serious complication of a percutaneous liver biopsy usually occurring within the first two to three hours after the procedure. Ultrasound can be routinely used immediately before the biopsy to localize the site and after the biopsy to make sure that there is no evidence of postprocedure hemorrhage. If hemorrhage is suspected, arrangements for blood, platelet, and plasma transfusions are made. The interventional radiologists and the surgeons should be alerted that angiography or intraabdominal surgery may be necessary. In most cases, post-procedure hemorrhage can be managed conservatively.

Liver biopsies are usually performed on an outpatient basis provided that: 1) a reliable individual is able to escort the patient home and is able to stay with the patient overnight after the biopsy, 2) the biopsy was performed in a facility with an approved laboratory, a blood-banking unit, and an inpatient unit. Patients who have a liver biopsy should be monitored for 4-6 hours after the procedure. Ultrasonography, may also reduce the risk of complications from the liver biopsy by identifying clinically silent mass lesions and can define the hepatic anatomy relative to the gall bladder, lungs and kidneys.

In the event of contraindications to a percutaneous liver biopsy (i.e. uncooperative patient, history of unexplained bleeding, tendency to bleed [prothrombin time > 3-5 sec more than control, platelet count <50,000/mm3, prolonged bleeding time (> 10 min), or use of nonsteroidal antiinflammatory drug within previous 7-10 days], suspected hepatic hemangioma or echinococcal cyst), the biopsy can be obtained through the transjugular approach. Liver biopsies can also be performed via the laparoscope, although the frequency with which this procedure is performed has decreased in recent years.