HCV infection treatment consideratios

HCV is a slowly progressive disease, usually requiring more than 20-40 years to progress to cirrhosis, but it may progress sooner in some patients, particularly among those who drink alcohol regularly. In non-cirrhotic patients, the short-term risk of developing a liver-related complication is low. Once a patient develops advanced cirrhosis, there is a higher likelihood of developing decompensated cirrhosis, including HCC, although the actual risk remains modest (<5% per year). Achieving SVR among patients with compensated cirrhosis reduces the risk of developing decompensated cirrhosis or HCC.
Patients with decompensated cirrhosis (Child-Turcotte-Pugh Class B or C; CTP score ≥7) have increased mortality, with median survival of 24 months or less. However, treatment options are limited for patients with decompensated cirrhosis. Treatment risks with interferon include infection and worsening hepatic function. The safety and efficacy data for sofosbuvir-based regimens among patients with decompensated cirrhosis are lacking. Since peginterferon is not recommended and no dosage recommendation can be given for simeprevir (if its use in combination with sofosbuvir were considered) in patients with decompensated cirrhosis, at the present time, the decision to treat and treatment follow-up of patients with decompensated cirrhosis should be made by an experienced and knowledgeable specialist.

Table 13. Diagnosis of Compensated Cirrhosis for the Purpose of Identifying Treatment Candidates

Method	Comments
Abbreviations: APRI = [(AST/upper limit of normal AST) x 100]/platelet count (109/L); FIB-4 = [Age (years) x AST]/platelet count (109/L) x ALT1/2; HALT-C cirrhosis score (see www.haltctrial.org/cirrhosis.html) *A low platelet count in the context of chronic HCV infection is predictive of histologic cirrhosis.
Clinical Findings	Physical exam findings (palpable left lobe, splenomegaly, palmar erythema) AND Low platelet count (<100,000/mm3)* AND Abdominal imaging findings (see below)
Abdominal Imaging Ultrasound Computed tomography (CT) Magnetic resonance imaging (MRI)	Surface abnormalities (e.g., nodularity, and left lobe/caudate lobe hypertrophy) are suggestive of cirrhosis. Features of portal hypertension (e.g., splenomegaly, recanalization of umbilical vein, collaterals) and ascites also are suggestive of cirrhosis.
Liver Fibrosis Imaging Vibration-controlled transient elastography (Fibroscan®) Acoustic radiation force impulse imaging (ARFI)	Both elastography and ARFI are FDA-approved, ultrasound-based techniques for estimating the extent of liver fibrosis. Fibroscan value of >12.5 kilopascals has been associated with histologic cirrhosis. ARFI value of >1.75 meters/second has been associated with histologic cirrhosis.
Serum Markers of Fibrosis/Cirrhosis APRI FIB-4 HALT-C cirrhosis score Fibrosure, Fibrotest, Fibrospect	APRI and FIB-4 scores are easily calculated using standard clinical labs. APRI >1.5 has been associated with advanced fibrosis (METAVIR F3); APRI >2.0 has been associated with cirrhosis (METAVIR F4) in the setting of chronic HCV infection. FIB-4 >3.25 has been associated with advanced fibrosis (METAVIR F3-F4) in the setting of chronic HCV infection. HALT-C cirrhosis score predicts likelihood of having cirrhosis based on standard clinical data. Fibrosure, Fibrotest, and Fibrospect are proprietary, costly serum fibrosis assays that are not recommended for routine use in the diagnosis of cirrhosis.
Liver Biopsy	Liver biopsy may be considered, but it is invasive and limited by potential sampling error. METAVIR or Batts-Ludwig stage 4 fibrosis (on a scale from 0 to 4) or Ishak stage 5 or 6 fibrosis (on a scale from 0 to 6) confirms the diagnosis of cirrhosis.

Diagnosis of Compensated Cirrhosis for the Purpose of Identifying Treatment Candidates (see Table 13): Noninvasive and invasive methods to determine the presence and stage of cirrhosis are continually evolving. Cirrhosis determination can be made using a histologic assessment of liver biopsy tissue. However, several limitations exist, namely, not all facilities offer this procedure, the quality of tissue is dependent upon the equipment and skill of the proceduralist; it is invasive, expensive, prone to sampling error and variability in histopathologic interpretation; and it carries a small risk of complications to the patient.
Serum markers: Routine blood tests can assist in identifying patients with advanced liver disease and, in some instances, predict the likelihood of developing decompensated disease or HCC. Serum markers of fibrosis (e.g., APRI, FIB-4, Fibrosure) may suggest the presence of advanced fibrosis or cirrhosis (Table 13). Similarly, the Ghany HALT-C score (www.haltctrial.org/cirrhosis.html) uses standard clinical data to predict the likelihood of a patient having cirrhosis. A score of >0.6 (i.e., >60%) is generally considered as an indication of cirrhosis. A Lok HALT-C HCC score greater than 3.25 (www.haltctrial.org/hccform.html) is associated with increased risk of developing hepatocellular carcinoma in the subsequent 3-5 years.
Platelet counts are an additional noninvasive tool to identify cirrhotic patients with more advanced cirrhosis. In the absence of hematopoietic disorders, patients with platelet counts of <150,000/mm3 have increased risk of developing HCC, whereas patients with platelet counts of <100,000/mm3 have an even higher risk of developing HCC.
Imaging: Findings of nodular liver or splenomegaly (>13 cm) on imaging (e.g., ultrasound, CT scan or MRI) suggest cirrhosis. Recently, the FDA approved two specialized ultrasound-based evaluations, vibration-controlled transient elastography and acoustic radiation force impulse imaging, to monitor liver fibrosis progression. These modalities have been correlated with stage of histologic fibrosis; cutoffs that correspond to histologic cirrhosis have been developed, but may vary by population studied.
Hepatocellular carcinoma: The following is based on expert opinion, given that minimal data are available. Achieving an SVR is likely to improve outcome among patients in whom treatment is expected to remove/ablate the entire tumor (i.e., "curative intent") (e.g., transplant, surgical resection, and, potentially, radiofrequency ablation or TACE of small HCC). Thus, sofosbuvir/ribavirin treatment (possibly in combination with peginterferon) in these patients is reasonable, particularly for those awaiting liver transplantation and for those with a CTP score <7, given the available clinical trial data in this population and FDA labeling. Among patients in whom HCC treatment is noncurative (i.e., palliative), treatment of HCV is unlikely to provide significant prolongation of life or improvement in symptoms, and is not recommended until evidence of survival benefit is available.

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