Candidates For Antiviral Therapy Research Articles

Direct oral anticoagulant plasma levels’ striking increase in severe COVID‐19 respiratory syndrome patients treated with antiviral agents: The Cremona experience

BackgroundAntiviral drugs are administered in patients with severe COVID‐19 respiratory syndrome, including those treated with direct oral anticoagulants (DOACs). Concomitant administration of antiviral agents has the potential to increase their plasma concentration. A series of patients managed in the Cremona Thrombosis Center were admitted at Cremona Hospital for SARS‐CoV‐2 and started antiviral drugs without stopping DOAC therapy. DOAC plasma levels were measured in hospital and results compared with those recorded before hospitalization. MethodsAll consecutive patients on DOACs were candidates for administration of antiviral agents (lopinavir, ritonavir, or darunavir). Plasma samples for DOAC measurement were collected 2to 4 days after starting antiviral treatment, at 12 hours from the last dose intake in patients on dabigatran and apixaban, and at 24 hours in those on rivaroxaban and edoxaban. For each patient, C‐trough DOAC level, expressed as ng/mL, was compared with the one measured before hospitalization. ResultsOf the 1039 patients hospitalized between February 22 and March 15, 2020 with COVID‐19 pneumonia and candidates for antiviral therapy, 32 were on treatment with a DOAC. DOAC was stopped in 20 and continued in the remaining 12. On average, C‐trough levels were 6.14 times higher during hospitalization than in the pre‐hospitalization period. ConclusionDOAC patients treated with antiviral drugs show an alarming increase in DOAC plasma levels. In order to prevent bleeding complications, we believe that physicians should consider withholding DOACs from patients with SARS‐CoV‐2 and replacing them with alternative parenteral antithrombotic strategies for as long as antiviral agents are deemed necessary and until discharge.

Simple predictors of nonresponse to direct-acting antivirals in chronic hepatitis C patients.

The introduction of direct acting antivirals (DAAs) has resulted in very high sustained virological response rates (SVR) in patients with chronic hepatitis-C (CHC). There are still a minority who fails to achieve SVR. This study aims to identify simple factors associated with nonresponse to DAAs using routine pretreatment workup. A retrospective study included 10 655 CHC patients who were candidates for anti-viral therapy. Pretreatment demographics, laboratory results, ultrasonography and FIB-4were obtained. At post-treatment week 4, 10 495 patients (98.5%) were responders and 160 (1.5%) were non-responders. About 50.6% of non-responders were males and 61.3% were cirrhotic. Non-responders had significantly higher baseline BMI, liver enzymes, AFP and a significantly lower albumin, platelet count by univariate analysis ((P < 0.001). Sex, previous treatment, BMI, liver cirrhosis, AST, Albumin and platelet counts were the independent predictors of non-response. At post-treatment week 12, HCV-PCR results were available only for 7259 patients and 210 (2.9%) were non-responders. 54.8% of non-responders were cirrhotic and 51.4% were males. Non-responders had significantly higher AST, AFP and INR and a significantly lower albumin level, platelet count by univariate analysis (P < 0.05). Sex, previous treatment, AST, Albumin, WBC and platelet counts were the independent predictors of non-response. SVR-4 among treatment naive patients was 98.6% while among treatment experienced was 96.8%. SVR-12 among treatment naive patients was 97.9% while among treatment experienced was 87.9%.Cirrhotics had SVR-4 rate 97.7% and SVR-12 rate 96.21%. Routine pre-treatment work up for HCV G4 patients receiving DAAs can help in prediction of non-response.

An expert consensus for the management of chronic hepatitis B in Asian Americans.

SummaryBackgroundHepatitis B virus (HBV) infection is common with major clinical consequences. In Asian Americans, the HBsAg carrier rate ranges from 2% to 16% which approximates the rates from their countries of origin. Similarly, HBV is the most important cause of cirrhosis, hepatocellular carcinoma (HCC) and liver related deaths in HBsAg positive Asians worldwide.AimTo generate recommendations for the management of Asian Americans infected with HBV.MethodsThese guidelines are based on relevant data derived from medical reports on HBV from Asian countries as well as from studies in the HBsAg positive Asian Americans. The guidelines herein differ from other recommendations in the treatment of both HBeAg positive and negative chronic hepatitis B (CHB), in the approach to HCC surveillance, and in the management of HBV in pregnant women.ResultsAsian American patients, HBeAg positive or negative, with HBV DNA levels >2000 IU/mL (>104 copies/mL) and ALT values above normal are candidates for anti‐viral therapy. HBeAg negative patients with HBV DNA >2000 IU/mL and normal ALT levels but who have either serum albumin <3.5 g/dL or platelet count <130 000 mm3, basal core promoter (BCP) mutations, or who have first‐degree relatives with HCC should be offered treatment. Patients with cirrhosis and detectable HBV DNA must receive life‐long anti‐viral therapy. Indications for treatment include pregnant women with high viraemia, coinfected patients, and those requiring immunosuppressive therapy. In HBsAg positive patients with risk factors, life‐long surveillance for HCC with alpha‐fetoprotein (AFP) testing and abdominal ultrasound examination at 6‐month intervals is required. In CHB patients receiving HCC treatments, repeat imaging with contrast CT scan or MRI at 3‐month intervals is strongly recommended. These guidelines have been assigned to a Class (reflecting benefit vs. risk) and a Level (assessing strength or certainty) of evidence.ConclusionsApplication of the recommendations made based on a review of the relevant literature and the opinion of a panel of Asian American physicians with expertise in HBV treatment will inform physicians and improve patient outcomes.

Sofosbuvir and simeprevir is effective for recurrent hepatitis C in liver transplant recipients.

Hepatitis C is the most common indication for liver transplantation (LT). Recurrent infection is universal and can lead to progressive liver disease. Widespread use of interferon-based therapy has been limited by intolerability and adverse effects. We retrospectively evaluated the safety, tolerability, and efficacy of sofosbuvir and simeprevir in the treatment of recurrent hepatitis C in adult (age >18) LT recipients. Seventy-six percent of the recipients were male and the mean age [±standard deviation (SD)] was 61 (±6.0) years. The mean time (±SD) from LT to treatment initiation was 71.8 (±77.1) months. Of the 26 patients with viral levels measured 4weeks after starting antiviral therapy, 58% were undetectable. At the end of therapy, viral load was undetectable in all transplant recipients. The 12week sustained viral response (SVR) was 93%. All recipients were able to complete therapy and no patients required growth factors of blood product transfusion during treatment. No patient required drug interruption of their immunosuppressant therapy. The use of sofosbuvir and simeprevir is efficacious, safe, and tolerable and should be considered in LT recipients with recurrent HCV who are candidates for antiviral therapy.

Liver Stiffness 1 Year After Transplantation Predicts Clinical Outcomes in Patients With Recurrent Hepatitis C

The value of transient elastography (TE) to assess clinical outcomes in hepatitis C recurrence after liver transplantation (LT) has not been explored so far. We studied 144 hepatitis C–infected and 48 non–hepatitis C virus (HCV)-infected LT recipients and evaluated the prognostic value of TE 1 year after transplantation to predict clinical decompensations and graft and patient survival. In HCV patients, cumulative probabilities of liver decompensation 5 years after LT were 8% for patients with liver stiffness measurement (LSM) <8.7 kilopascals (kPa) versus 47% for patients with LSM ≥ 8.7 kPa (p < 0.001). Five-year graft and patient cumulative survival were 90% and 92% in patients with LSM < 8.7 kPa (p < 0.001) and 63% and 64% in patients with LSM ≥ 8.7 kPa, respectively (p < 0.001). Patients with low LSM 1 year after LT had excellent outcomes independently from receiving antiviral treatment or achieving sustained virological response (SVR). In contrast, graft survival significantly improved in patients with LSM ≥ 8.7 kPa who achieved SVR. No association between outcomes and LSM at 12 months was observed in non-HCV patients. In conclusion, LSM 1 year after LT is a valuable tool to predict hepatitis C-related outcomes in recurrent hepatitis C and can be used in clinical practice to identify the best candidates for antiviral therapy.

Preparing the patient for success: Treat or wait?

Hepatitis C is a frequent cause of liver cirrhosis and, hepatocellular carcinoma worldwide. However, predicting clinical outcomes in patients with chronic hepatitis C is challenging. The risk of disease progression is not linear and can be associated with several factors. With the currently available therapies, around 70% of naïve patients, independently of hepatitis C virus genotype can achieve a sustained virologic response. Consequently, all hepatitis C virus patients are candidates for antiviral therapy. The decision to treat a patient with chronic hepatitis C virus infection is based on several factors, including the natural history of the disease, the stage of fibrosis, and the efficacy and adverse effects related to therapy. The decision to treat immediately or wait for a new drug is more difficult and should be tailored to each patient, taking into account the patient's characteristics, the risk of disease progression, the patient's wishes, and the experience of the attending physician.

Nucleos(t)ide Analogues Therapy for Chronic Hepatitis B in Taiwan: Short-Term Versus Long-Term

Chronic hepatitis B (CHB) remains an important health issue in Taiwan. The major candidates for antiviral therapy are HBeAg-positive and -negative CHB patients, and individuals with compensated or decompensated cirrhosis. Lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate (TDF) are the currently available nucleos(t)ide analogues (NA). Entecavir and TDF are recommended as the first-line agents for long-term use. The therapeutic endpoints recommended by the Asian Pacific Association for the Study of the Liver treatment guidelines have been adopted for clinical practice. Only a small number of patients qualify for short-term NA therapy; the majority of patients need long-term treatment. Current therapeutic endpoints confer off-therapy durability in approximately 50 % of patients. Patients with cirrhosis should receive long-term NA therapy. The use of serum HBsAg level as a guide for cessation of NA therapy requires further investigation.

Severe Neutropenia in Patients with Chronic Hepatitis C: A Benign Condition

Background/Aims: Patients with chronic hepatitis C virus (HCV) infection may develop neutropenia, which can delay or prevent treatment. Severe neutropenia, absolute neutrophil counts (ANC) ≤0.500 × 10⁹/l, is a rare finding, with only two isolated reports published in the literature. The aim of this study was to evaluate the incidence and natural history of severe neutropenia in hepatitis C patients. Methods: The records of 685 patients with active HCV were reviewed to identify those with severe neutropenia. The laboratory parameters and clinical history data of patients with severe neutropenia were then compared to a cohort of patients with HCV patients who had the more common minor neutropenia (ANC = 1.000–1.500 10⁹/l). Results: There was no significant difference in race, MELD (Model for End Stage Liver Disease) scores, portal hypertension, splenomegaly, viral load, viral type, or hemoglobin or platelet levels. Neither group suffered serious systemic infections. Conclusions: Severe neutropenia in HCV patients is underreported and not associated with serious HCV complications such as elevated MELD score or cirrhosis. Serious infection is rare and patients respond well to granulocyte colony-stimulating factor. Severely neutropenic patients with HCV appear to have a benign course and may be candidates for antiviral therapy.

Checkmate to liver biopsy in chronic hepatitis C?

Liver biopsy (LB) has traditionally been considered the gold standard for pretreatment evaluation of liver fibrosis in patients with chronic hepatitis C (CHC). However, LB is an invasive procedure with several shortcomings (intra- and interobserver variability of histopathological interpretation, sampling errors, high cost) and the risk of rare but potentially life-threatening complications. In addition, LB is poorly accepted by patients and it is not suitable for repeated evaluation. Furthermore, the prevalence of CHC makes LB unrealistic to be performed in all patients with this disease who are candidates for antiviral therapy. The above-mentioned drawbacks of LB have led to the development of noninvasive methods for the assessment of liver fibrosis. Several noninvasive methods, ranging from serum marker assays to advanced imaging techniques, have proved to be excellent tools for the evaluation of liver fibrosis in patients with CHC, whereas the value of LB as a gold standard for staging fibrosis prior to antiviral therapy has become questionable for clinicians. Despite significant resistance from those in favor of LB, noninvasive methods for pretreatment assessment of liver fibrosis in patients with CHC have become part of routine clinical practice. With protease inhibitors-based triple therapy already available and substantial improvement in sustained virological response, the time has come to move forward to noninvasiveness, with no risks for the patient and, thus, no need for LB in the assessment of liver fibrosis in the decision making for antiviral therapy in CHC.

Severe Neutropenia in Patients with Chronic Hepatitis C Not on Antiviral Therapy At the Memphis Veteran's Affairs Medical Center

Abstract 4733Abstract: We reviewed the records of 685 patients evaluated for treatment of chronic hepatitis C virus (HCV) at the Veteran’s Affairs Medical Center in Memphis, TN in 2010. We identified six cases of severe neutropenia (defined as an absolute neutrophil count <500 x103/dL), in the absence of medications known to cause neutropenia such as interferon. None had concomitant HIV infections. Bone marrow biopsies were performed in three of the six patients and were negative for malignancy or abnormal myelopoesis. In this case series report, we compare laboratory parameters and clinical histories of these six patients to a similar cohort of chronic hepatitis C patients with at least one documented absolute neutrophil count (ANC) between 1000 x103/dL and 1500 × 103/dL. The two groups differed only in ANC and frequency of anti-nuclear antibody positivity. There was no significant difference in race, MELD scores, viral load, viral type, hemoglobin levels or platelet levels. Neither group suffered serious systemic infections. There was no evidence that the severe neutropenia was related to portal hypertension or splenomegaly. In our series, patients with severe neutropenia in the setting of chronic HCV had a benign course that did not lead to severe infections and responded to granulocyte colony stimulating factor. This opens the question of whether these patients may be candidates for antiviral therapy. Disclosures:No relevant conflicts of interest to declare.

The Management of Chronic Hepatitis B in Asian Americans

Hepatitis B virus (HBV) infection is common with major clinical consequences worldwide. In Asian Americans, the HBsAg carrier rate ranges from 7 to 16%; HBV is the most important cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Patients are first diagnosed at different stages of clinical disease, which is categorized by biochemical and virologic tests. Patients at risk for liver complications should be identified and offered antiviral therapy. The two antiviral agents recommended for first-line treatment of chronic hepatitis B (CHB) are entecavir and tenofovir. The primary goal of therapy is sustained suppression of viral replication to achieve clinical remission, reverse fibrosis, and prevent and reduce progression to end-stage liver disease and HCC. Asian patients with chronic hepatitis, either HBeAg-positive or -negative, with HBV DNA levels >10(4)copies/mL (>2,000IU/mL) and alanine aminotransferase (ALT) values above normal are candidates for antiviral therapy. HBeAg-negative patients with HBV DNA >10(4)copies/mL (>2,000IU/mL) and normal ALT levels but who have either serum albumin ≤3.5g/dL or platelet count ≤130,000mm(3), basal core promoter mutations, or who have first-degree relatives with HCC should be offered treatment. Patients with cirrhosis and detectable HBV DNA must receive antiviral therapy. Considerations for treatment include pregnant women with high viremia, coinfected patients, and those requiring immunosuppressive therapy. In HBsAg-positive patients with risk factors, lifelong surveillance for HCC with alpha-fetoprotein testing and abdominal ultrasound examination at 6-month intervals is required. These recommendations are based on a review of relevant literature and the opinion of a panel of Asian American physicians with expertise in hepatitis B treatment.

Effects of Interferon Alpha on Parathyroid Gland in Chronic Hepatitis B and C: An Observational Study

Introduction: Serum alanine aminotransferase (ALT) remains one of three principal parameters used by AASLD, EASL, and APASL guidelines to identify candidates for antiviral therapy. Whereas individuals who are immunotolerant or inactive carriers can be safely monitored, and individuals with immune active disease clearly warrant antiviral therapy, individuals with elevated HBV DNA but normal ALT represent a subgroup for whom treatment remains controversial. Aim: We conducted a systematic review and meta-analysis to evaluate the prevalence of significant histology (grade 2 activity or stage 2 fibrosis) in individuals with chronic HBeAg positive or negative infection, elevated HBV DNA, and persistently normal serum ALT, defined as at minimum two consecutive normal values based on laboratory reference range or standarized Prati criteria six months apart. Methods: Searches of literature databases and meeting abstracts 2000-2010 were performed by two independent reviewers through September 2010. Observational studies with at least 30 patients who underwent a liver biopsy within six months of index serum ALT were included. After adjudication of a third expert reviewer, nine studies meeting quality criteria were identified, including 849 patients. Results: Pooled analyses revealed that the prevalence of significant histologic disease was 22.5% overall, 12.2% in HBeAg+ patients, and 23.7% in HBeAgpatients. Additional predictors of significant histology included HBV DNA, definitions of normal serum ALT, and number of normal serum ALT values. Conclusions: A significant proportion of patients with persistently normal serumALT and high HBVDNAhave histologic evidence of significant disease, and may represent potential candidates for antiviral therapy. Additional studies to clarify individuals to be targeted for liver biopsy and antiviral therapy in this setting are warranted.

376 SYSTEMATIC REVIEW AND META-ANALYSIS: PREVALENCE OF SIGNIFICANT HISTOLOGIC DISEASE IN CHRONIC HEPATITIS B INFECTION, HIGH HBVDNA, AND PERSISTENTLY NORMAL SERUM ALT (PNALT)

Introduction: Serum alanine aminotransferase (ALT) remains one of three principal parameters used by AASLD, EASL, and APASL guidelines to identify candidates for antiviral therapy. Whereas individuals who are immunotolerant or inactive carriers can be safely monitored, and individuals with immune active disease clearly warrant antiviral therapy, individuals with elevated HBV DNA but normal ALT represent a subgroup for whom treatment remains controversial. Aim: We conducted a systematic review and meta-analysis to evaluate the prevalence of significant histology (grade 2 activity or stage 2 fibrosis) in individuals with chronic HBeAg positive or negative infection, elevated HBV DNA, and persistently normal serum ALT, defined as at minimum two consecutive normal values based on laboratory reference range or standarized Prati criteria six months apart. Methods: Searches of literature databases and meeting abstracts 2000-2010 were performed by two independent reviewers through September 2010. Observational studies with at least 30 patients who underwent a liver biopsy within six months of index serum ALT were included. After adjudication of a third expert reviewer, nine studies meeting quality criteria were identified, including 849 patients. Results: Pooled analyses revealed that the prevalence of significant histologic disease was 22.5% overall, 12.2% in HBeAg+ patients, and 23.7% in HBeAgpatients. Additional predictors of significant histology included HBV DNA, definitions of normal serum ALT, and number of normal serum ALT values. Conclusions: A significant proportion of patients with persistently normal serumALT and high HBVDNAhave histologic evidence of significant disease, and may represent potential candidates for antiviral therapy. Additional studies to clarify individuals to be targeted for liver biopsy and antiviral therapy in this setting are warranted.

Histologic Disease in Patients with Chronic Hepatitis B, High HBV DNA, and Normal Alanine Aminotransferase Levels

Recent advances in the treatment of hepatitis B virus (HBV) infection have presented new options as well as challenges. Serum alanine aminotransferase (ALT) continues to be one of the three principal parameters used by all existing treatment guidelines to identify candidates for antiviral therapy. Although there is little controversy that inactive carriers and young immune tolerant patients can be monitored without antiviral therapy, and that antiviral therapy should be initiated in immune active patients with elevated HBV DNA ant ALT levels, not all guidelines agree on the management of older individuals with elevated HBV DNA but normal ALT levels who may no longer be immune tolerant and who have significant histologic disease. These patients may benefit from antiviral therapy, but distinguishing them from the true immune tolerant patient is challenging. This article reviews the natural history of chronic hepatitis B, the evolving concept of a “normal”ALT level, and recent studies examining liver histology in patients with chronic HBV infection, high HBV DNA levels, and normal ALT levels.

Review article: Hepatitis B and dialysis

The incidence of hepatitis B virus (HBV) infection in dialysis populations has declined over recent decades, largely because of improvements in infection control and widespread implementation of HBV vaccination. Regardless, outbreaks of infection continue to occur in dialysis units, and prevalence rates remain unacceptably high. For a variety of reasons, dialysis patients are at increased risk of acquiring HBV. They also demonstrate different disease manifestations compared with healthy individuals and are more likely to progress to chronic carriage. This paper will review the epidemiology, modes of transmission and diagnosis of HBV in this population. Prevention and treatment will be discussed, with a specific focus on strategies to improve vaccination response, new therapeutic options and selection of patients for therapy.

Hepatitis B – new diagnostic algorithms, monitoring treatment and drug resistance

Several recent advances have helped to redesign treatment algorithms for chronic hepatitis B. The recognition that there was a biological gradient of serum hepatitis B virus (HBV) DNA associated with an increased risk of liver disease has allowed more patients to be identified as candidates for antiviral therapy. The limited success of currently available therapy has prompted international liver societies to propose treatment guidelines. Unfortunately, treatment with nucleoside and nucleotide analogues has been compromised by the seemingly inevitable development of drug resistance. Drug resistance is of particular concern due to the increasing number of agents with potential for cross-resistance, which emphasises the importance of sensitive assays for viral load and for defining genotypic resistance. Other promising markers for determining treatment eligibility and predicting response include HBV genotype and the measurement of intrahepatic HBV replicative forms. Most recently, data from clinical trials suggests a possible role for on-treatment quantification of hepatitis B surface antigen during interferon-based therapy in predicting virological outcome. At present, ongoing research is defining the clinical utility of these markers in the management of chronic hepatitis B.

Incidence of hepatocellular carcinoma in hepatitis C carriers with normal alanine aminotransferase levels

This study sought to identify the independent risk factors involved in the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection who have normal alanine aminotransferase (ALT) levels. A total of 519 patients with average ALT integration values less than or equal to 40 IU/L over 10 years were included. Baseline ultrasound was done in all patients and 68 patients underwent liver biopsy at the start of this study. Factors associated with the cumulative incidence of HCC were determined. HCC occurred in 48 of 519 patients (9.2%). The following factors were significantly associated with the incidence of HCC: age>65 years (adjusted hazard ratio: 2.006 [95% confidence interval: 1.078-3.733]), ALT>20 IU/L (6.242 [1.499-25.987]), platelet count<15.0x10(4)/m(3) (2.675 [1.407-5.085]), total bilirubin>1.2mg/dL (2.798 [1.257-6.228]), ALP>338 IU/L (2.486 [1.327-4.657]), and total albumin<3.5g/dl (2.707 [1.177-6.223]). The 5- and 10-year cumulative incidences of HCC were 4.4% and 26.5% in patients with ALT>20 IU/L and platelet count<15.0x10(4)/m(3), respectively. High ALT level and low platelet count are closely associated with the development of hepatocarcinogenesis. Therefore, individuals within this group are candidates for antiviral therapy.

Ganciclovir: Antiviral Therapy for Congenital Cytomegalovirus

CYTOMEGALOVIRUS (CMV), a member of the herpesvirus family, is the most common virus passed from the mother to the fetus. According to the Centers for Disease Control and Prevention (CDC), approximately 1 in 150 children is born with congenital CMV infection.1 Neonates may also acquire CMV during delivery, via blood transfusions, or through breast milk. Both prenatally and perinatally infected infants are at risk for developing short-term effects and long-term sequelae and are candidates for antiviral therapy.2 Each year, approximately 8,000 children suffer permanent disabilities secondary to CMV infection.1

Abstract B123: Stopping a silent killer in the underserved Asian community: A novel liver cancer prevention clinic

Abstract B123 Asian and Pacific Islanders bear a disproportionate burden of liver disease caused by chronic hepatitis B virus (HBV) infection, which is associated with a 25% risk of death from cirrhosis or liver cancer. However, few community based programs exist to tackle this serious public health problem among low income, uninsured Asian and Pacific Islander immigrants. The Hep B Free Clinic is a student-run grassroots organization that focuses on HBV and liver cancer prevention in one of the nation’s largest immigrant communities: San Jose, California. From 2007-2008, we provided free HBV serological screening to 510 patients. For chronically infected patients who elected to undergo follow up monitoring, a series of blood tests were given to evaluate for liver damage (alanine transaminase, ALT), a liver cancer marker (alpha-fetoprotein, AFP), and HBV replication (HBV DNA levels). Of those screened, 17% were chronically infected. Remarkably, one-third (33%) of infected patients were unaware that they were infected. Of those chronically infected, 100% showed signs of active liver damage as measured by elevated ALT, and 9% had elevated AFP tumor markers for hepatocellular carcinoma. Nearly one-quarter (24%) of those chronically infected carried HBV DNA levels that met the criteria for treatment. Patients who were candidates for antiviral therapy were signed up for free drug assistance programs, and those requiring triphasic CT scans for possible liver cancer were referred. Uninfected patients lacking protective HBV antibodies were provided free vaccinations. Our striking findings call for more aggressive liver cancer prevention in this community, including universal screening for HBV. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B123.

Compensated hepatitis C: unenhanced MR imaging correlated with pathologic grading and staging

We prospectively examined unenhanced MR imaging findings in relation to pathologic fibrosis, inflammation and steatosis in patients with compensated chronic hepatitis C viral infection (HCV). Unenhanced MRI at 1.5 T was obtained within one month of core liver biopsy in 64 consecutive candidates for antiviral therapy for compensated HCV. Two pathologists independently graded inflammatory activity index (HAI) and steatosis, and staged fibrosis (grades 0-6). Morphologic MRI findings of cirrhosis, periportal lymph nodes, and MR fat signal ratio from dual gradient echo images were assessed independently by two radiologists blinded to clinical data. MRI and laboratory liver function results were correlated with pathologic results, using Spearman correlation coefficient and stepwise multiple regression. MR fat signal ratio correlation coefficient with pathologic steatosis was 0.71 (p < 0.0001). Coefficients with fibrosis stage were highest for surface nodularity (r (s) = 47, p < 0.0001) and expanded gallbladder fossa (r (s) = 0.42, p = 0.0006). Coefficients with HAI were highest for lymph node size (r (s) = 0.355, p = 0.0040), surface nodularity (r = 0.47, p < 0.0001), expanded gallbladder fossa (r = 0.332, p = 0.0073), and caudate/right lobe ratio (r = 0.326, p = 0.0110). Combined lab and MRI variables provided the best prediction of fibrosis stage (r (2) = 0.656) and HAI (r (2) = 0.597). A combination of MRI and laboratory findings was most predictive of fibrosis and inflammation.