Albert D. Min

Sensitivity of commonly available screening tests in detecting hepatocellular carcinoma in cirrhotic patients undergoing liver transplantation

OBJECTIVE:Recognition of hepatocellular carcinoma (HCC) is important in the management of patients awaiting liver transplantation. HCCs >5 cm in diameter are at high risk to recur after transplant. The goal of this study was to assess the sensitivity of the diagnostic tests employed in a pretransplant screening program.METHODS:The study is a retrospective analysis of charts of 106 consecutive adults transplanted over a 1-yr period. All patients had ultrasonography (US), computerized tomography (CT), and serum alpha fetoprotein (AFP) testing within 6 months of transplantation. Radiographic reports were subdivided into low-risk and high-risk groups, based upon level of suspicion for HCC. The results were compared to explant pathology.RESULTS:Pathological analysis of 106 explants revealed HCC in 19 patients. High-risk US exams had a positive predictive value (PPV) of 0.69 and a negative predictive value (NPV) of 0.91 in the diagnosis of HCC. High-risk CT exams had a PPV of 0.67 and an NPV of 0.90. When patients had either a high-risk US or a high-risk CT, there was a PPV of 0.59 and an NPV of 0.83. Of the 19 patients with HCC, three had high-risk US and low-risk CT; two had high-risk CT and low-risk US. Four patients, all with HCC <4 cm, had low-risk US, CT, and serum AFP.CONCLUSIONS:US, CT, and serum AFP, as single tests, are insensitive for detection of HCC in the cirrhotic liver. However, they are highly specific. Sensitivity and specificity for US are comparable to those for CT. Given its lower cost, US is preferable to CT for routine screening of HCC in patients with end-stage liver disease undergoing liver transplantation.

A Randomized Trial of Pegylated Interferon α-2b Plus Ribavirin in the Retreatment of Chronic Hepatitis C

OBJECTIVES:The efficacy of combination therapy with pegylated interferon (PEG IFN) α plus ribavirin (RBV) in the retreatment of chronic hepatitis C (CHC) in patients who previously failed combination standard IFN plus RBV or IFN monotherapy has not been well established.METHODS:Three hundred and twenty-one CHC patients including virologic nonresponders to combination IFN plus RBV (n = 219) or IFN monotherapy (n = 47), and relapsers to combination therapy (n = 55) were randomized to receive PEG IFN α-2b 1.5 μg/kg per wk plus RBV 800 mg per day (Regimen A, n = 160) or PEG IFN α-2b 1.0 μg/kg per wk plus RBV 1,000–1,200 mg per day (Regimen B, n = 161) for 48 wks.RESULTS:Sustained virologic response (SVR) occurred in 16% of the overall study population (Regimen A vs B, 18% vs 13%, p = 0.21), in 8% of the combination therapy nonresponders (10% vs 6%, p = 0.35), in 21% of the IFN monotherapy nonresponders (16% vs 27%, p = 0.35), and in 42% of the combination therapy relapsers (50% vs 32%, p = 0.18). In nonresponders to prior combination therapy, HCV ribonucleic acid levels <100,000 copies/mL at the end of the prior treatment course were associated with an increased SVR compared with levels ≥100,000 copies/mL (21% vs 5%, p = 0.002). In the overall study population, genotype 1 patients had lower SVR rates than others (14% vs 33%, p = 0.01), and African Americans had lower SVR than Caucasians (4% vs 18%, p = 0.01).CONCLUSION:Combination therapy with PEG IFN α-2b plus RBV is more effective in patients who relapsed after combination standard IFN plus RBV than in nonresponders to either combination therapy or IFN monotherapy. There was no significant effect of dosing regimen.

Accuracy and significance of computed tomographic scan assessment of hepatic volume in patients undergoing liver transplantation.

BACKGROUND A small liver volume is considered to be a poor prognostic factor in cirrhosis, often indicative of advanced liver disease. Radiologic assessment of liver volume before liver transplant is routinely performed in many transplant centers. We sought to assess the accuracy and significance of computed tomographic (CT) scanning in hepatic volumetric analysis by correlating CT-derived estimation of liver volume with that of corresponding liver explants. METHODS A chart review of all patients aged 17 years or older undergoing liver transplant at Mount Sinai Medical Center between 1989 and 1995 was performed. Each patient underwent conventional CT scanning with measurement of liver volume (CTLV). Recipient liver volume (RLV) was defined as weight of liver explant after all attached ligaments, portal structures, and gallbladder were dissected free. Expected liver volume was calculated pretransplant based on age, gender, height, and weight. Patients were categorized into three groups based on etiology of liver disease: (1) hepatocellular (e.g., viral hepatitis, alcohol-related), (2) cholestatic (e.g., primary biliary cirrhosis), and (3) cryptogenic. The ratio of CTLV to RLV was used as a measure of the accuracy of CT volumetric analysis. RESULTS A total of 579 patients was studied (group 1=376, group 2=139, group 3=64). All three groups were statistically similar with regard to age, prothrombin time and total bilirubin. Median CT liver volume was 1308 ml (range: 338-3847), 1651 ml (range: 641-3861), and 1210 ml (range: 348-2575) in groups 1-3, respectively; median ratio of CTLV to RLV was 1.02 (range: 0.50-2.31), 1.05 (range: 0.52-2.22), and 1.05 (range: 0.50-1.56) for groups 1-3, respectively. When RLV was small, it tended to be overestimated by CTLV. In contrast, when RLV was large, it was often underestimated. Clinical features such as history of esophageal variceal bleed, encephalopathy or ascites, and laboratory data did not influence accuracy of CT volumetric analysis. CONCLUSIONS CT-derived estimation of liver volume appears to correlate closely with actual weight of liver explant regardless of the etiology of chronic liver disease. With extremes in CT volumetric analysis, actual liver volume tends to be under- or overestimated. For patients with end-stage liver disease, both CT-derived and actual liver volume are greater in cholestatic than in hepatocellular disorders.

A Randomized Trial of a Hepatitis Care Coordination Model in Methadone Maintenance Treatment

OBJECTIVES We evaluated the efficacy of a hepatitis care coordination intervention to improve linkage to hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccination and clinical evaluation of hepatitis C virus (HCV) infection among methadone maintenance patients. METHODS We conducted a randomized controlled trial of 489 participants from methadone maintenance treatment programs in San Francisco, California, and New York City from February 2008 through June 2011. We randomized participants to a control arm (n = 245) and an intervention arm (n = 244), which included on-site screening, motivational-enhanced education and counseling, on-site vaccination, and case management services. RESULTS Compared with the control group, intervention group participants were significantly more likely (odds ratio [OR] = 41.8; 95% confidence interval [CI] = 19.4, 90.0) to receive their first vaccine dose within 30 days and to receive an HCV evaluation within 6 months (OR = 4.10; 95% CI = 2.35, 7.17). A combined intervention adherence outcome that measured adherence to HAV-HBV vaccination, HCV evaluation, or both strongly favored the intervention group (OR = 8.70; 95% CI = 5.56, 13.61). CONCLUSIONS Hepatitis care coordination was efficacious in increasing adherence to HAV-HBV vaccination and HCV clinical evaluation among methadone patients.

Survival and Risk of Recidivism in Methadone-Dependent Patients Undergoing Liver Transplantation

Cirrhosis resulting from hepatitis C virus is presently the most common indication for liver transplantation (OLT) in the United States. A number of U.S. transplant centers require cirrhotics who are using methadone to discontinue it before proceeding with OLT. We sought to examine the outcomes of those patients who had undergone OLT at the Mount Sinai Medical Center.

Long-term safety and tolerability of entecavir in patients with chronic hepatitis B in the rollover study ETV-901

Objective: To review long-term safety data from the rollover study ETV-901, focusing on adverse events (AEs) with a potential nucleos(t)ide association. Methods: The open-label study ETV-901 (AI463901) assessed the safety of entecavir in chronic hepatitis B patients who received entecavir, lamivudine or adefovir monotherapy in previous entecavir Phase II/III studies. Long-term cumulative safety results are based on reported AEs, regardless of causal relationship. Results: Median exposure to entecavir in study ETV-901 was 184 weeks. Commonly reported AEs (≥ 10%) were upper respiratory tract infection, headache and nasopharyngitis. Most AEs were mild to moderate; 203 (19%) patients reported grade 3 – 4 AEs, with 45 (4%) considered related to entecavir. There were 14 (1%) discontinuations due to AEs. On-treatment alanine aminotransferase (ALT) flares were reported in 32 (3%) patients and were associated with a reduction in hepatitis B virus DNA of more than 2 log10 copies/ml in 25/32 patients. AEs potentially associated with nucleos(t)ide analogs were infrequent, the most common being myalgia (n = 54; 5%) and neuropathy-related AEs (hypoparesthesia and hyperparesthesia, polyneuropathy; n = 42; 4%). Conclusions: Long-term administration of entecavir was associated with low rates of serious AEs, discontinuations due to AEs and ALT flares. AEs potentially associated with nucleos(t)ide use occurred at low rates.

Entecavir Safety and Effectiveness in a National Cohort of Treatment-Naïve Chronic Hepatitis B Patients in the US - the ENUMERATE study

Entecavir (ETV) has been shown to be safe and efficacious in randomised controlled trials in highly selected patients with hepatitis B virus (HBV) infection.

Chronic Hepatitis C Virus and Celiac Disease, is there an Association?

Celiac disease (CD) has been epidemiologically associated with chronic hepatitis C (HCV), and CD activation after the initiation of interferon (IFN-α) in patients with HCV is documented. However, clear association of CD and HCV is lacking. A prospectively maintained database of 878 CD patients showed a prevalence of 0.68% (six patients). Symptoms of diarrhea, weight loss, and depression prompted the diagnosis of CD during or after IFN-α therapy in four cases. Also, 294 subjects with liver disease (195 with HCV, 80 normal controls and 19 disease controls) were prospectively screened for CD. The mean age of the subjects was 50.1 years (SD 12.3), 58% males:42% females. A total of 30% received IFN-α therapy (16% at the time of testing for CD). Two HCV patients (1%) had positive tTG-IgA but these had negative endomysial antibody (EMA) and normal duodenal biopsies. CD prevalence is not increased in patients with HCV. Routine screening of CD in HCV patients is not warranted, however, the presence of CD should be considered in the setting of clinical deterioration during or after IFN-α therapy.

Outcome of hepatitis C patients with and without hepatocellular carcinoma undergoing liver transplant

Objective:Hepatitis C virus (HCV) infection is associated with development of hepatocellular carcinoma (HCC). The aim of this study was to examine clinical characteristics and outcome of patients with HCV with or without HCC undergoing liver transplant.Methods:We reviewed the charts of all 55 patients transplanted between November 1990 and December 1996 for HCV cirrhosis with HCC and compared them with a control group of HCV patients without HCC. Patients with a history of alcohol abuse or HBsAg positivity were excluded. There were 37 men and 18 women, with a mean age of 57.6 yr (range, 19–70 yr) in the HCC group.Results:There was no significant difference between the HCC and nonHCC groups regarding Childs class or United Network for Organ Sharing (UNOS) status at the time of transplant. Twenty-six (45%) patients were diagnosed or suspected of having HCC before transplant. Twenty-five patients (45.5%) had a single focus of HCC. Fourteen percent (seven of 50) of the patients with HCC had been treated with interferon, whereas 12% (six of 52) of patients in the nonHCC group had received interferon. Duration of interferon therapy ranged from 1 to 9 months. All interferon treatment occurred within 5 yr of transplant. A history of intravenous drug use or transfusion was identified in 37 (67%) of HCC patients. Thirty-two patients (58%) without HCC had a parenteral exposure. There was no significant difference in patient or graft survival rates between the patients with and without HCC.Conclusion:Approximately one-half of HCC was not detected before liver transplant. There was no significant difference in the mode of transmission, clinical status at the time of transplant, or outcome between the HCV patients with and without HCC.

A long-term study of the effects of antiviral therapy on survival of patients with HBV-associated hepatocellular carcinoma (HCC) following local tumor ablation.

The ultimate goal of antiviral therapy for chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC). Earlier we reported favorable effects of antiviral therapy on survival of HCC patients following curative tumor ablation (Int J Cancer online 14 April 2010; doi: 10.1002/ijc.25382). It was the first observation made in the United States. We now report 12 year follow‐up of this patient group. CHB patients with no prior antiviral therapy with a single HCC (≤7 cm) were studied. All patients underwent local tumor ablation as their first option. Patients diagnosed before 1999 received no antiviral treatment while those diagnosed after 1999 received antiviral treatment. Survival between the treated and untreated groups was compared. Among 555 HCC patients seen at our clinic between 1991 and 2013, 25 subjects were eligible. Nine subjects (all male patients, median age 53 years [46–66]) did not receive antiviral therapy while 16 (14 male patients, median age 56 years [20–73]) received treatment. Between the two groups, there was no difference in their median tumor size and levels of alpha‐fetoprotein and albumin. However, the survival was significantly different (P = 0.001): the median survival of the untreated was 16 months (3–36 months) while that of the treated was 80 months (15–152 months). Fourteen of 16 treated patients are alive to date with two longest survivors alive for ≥151 months. In conclusion, concomitant antiviral therapy for CHB patients with HCC reduces and prevents new/recurrent tumor and improves survival. This novel treatment strategy offers an alternative to liver transplantation in patients with HBV‐associated HCC.