Background and Aims: The outcome of patients with hepatocellular carcinoma (HCC) remains poor because of late diagnosis. The aim of this study was to compare the accuracy of alpha fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) in the early diagnosis of HCC. Methods: Among 1031 patients randomized in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) Trial, a nested case-control study of 39 HCC cases (24 early stage) and 77 matched controls was conducted to compare the performance of AFP and DCP. Testing was performed on sera from 12 months prior (month −12) to the time of HCC diagnosis (month 0). Results: The sensitivity and specificity of DCP at month 0 was 74% and 86% at a cutoff of 40 mAU/mL and 43% and 100% at a cutoff of 150 mAU/mL. The sensitivity and specificity of AFP at month 0 was 61% and 81% at a cutoff of 20 ng/mL and 22% and 100% at a cutoff of 200 ng/mL. At month −12, the sensitivity and specificity at the low cutoff was 43% and 94% for DCP and 47% and 75% for AFP. Combining both markers increased the sensitivity to 91% at month 0 and 73% at month 12 but the specificity decreased to 74% and 71%. Diagnosis of early HCC was triggered by surveillance ultrasound in 14, doubling of AFP in 5 and combination of tests in 5 patients. Conclusions: Biomarkers are needed to complement ultrasound in the detection of early HCC but neither DCP nor AFP is optimal.

Background & Aims Interferon reportedly decreases the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. The Hepatitis C anti-viral long-term treatment against cirrhosis (HALT-C) trial showed that 4 years of maintenance therapy with peginterferon does not reduce liver disease progression. We investigated whether peginterferon decreases the incidence of HCC in the HALT-C cohort over a longer post-treatment follow-up period. Methods The study included 1,048 patients with chronic Hepatitis C (Ishak fibrosis scores ≥3) who did not have a sustained virological response (SVR) to therapy. They were randomly assigned to groups given a half-dose of peginterferon or no treatment (controls) for 3.5 years and followed for a median 6.1 (maximum 8.7) years. Results Eighty-eight patients developed HCC (68 definite, 20 presumed): 37/515 that were given peginterferon (7.2%) and 51/533 controls (9.6%; P=0.24). There was a significantly lower incidence of HCC among patients given peginterferon therapy who had cirrhosis, but not fibrosis, based on analysis of baseline biopsy samples. After 7 years, the cumulative incidences of HCC in treated and control patients with cirrhosis were 7.8% and 24.2%, respectively (hazard ratio [HR]=0.45; 95% confidence interval [CI]: 0.24–0.83); in treated and control patients with fibrosis they were 8.3% and 6.8%, respectively (HR=1.44; 95% CI: 0.77–2.69). Treated patients with a ≥2-point decrease in the histologic activity index, based on a follow-up biopsy, had a lower incidence of HCC than those with unchanged or increased scores (2.9% vs. 9.4%; P=0.03). Conclusions Extended analysis of the HALT-C cohort showed that long-term peginterferon therapy does not reduce the incidence of HCC among patients with advanced hepatitis C who did not achieve SVRs. Patients with cirrhosis who received peginterferon treatment had a lower risk for HCC than controls.

BACKGROUND & AIMS With the limited efficacy of current therapy for chronic hepatitis C, modifiable risk factors for liver disease progression are important to identify. Because obesity is associated with liver disease, we examined the effects of weight-related conditions on disease outcomes in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. METHODS Of 1050 patients, 985 could be evaluated for predefined progression of liver disease not related to hepatocellular carcinoma. Clinical outcomes were determined over 3.5 years for all patients and progression to cirrhosis on protocol biopsy among patients who had bridging fibrosis (56.5% of cohort) at entry. RESULTS At study entry, median body mass index was high (29.2 kg/m2) and accompanied by other weight-related conditions, including diabetes (24.9%), high median waist circumference, and insulin resistance (by updated homeostasis model assessment of insulin resistance; HOMA2-IR). Among noninvasive measures, HOMA2-IR was most strongly associated with outcomes with hazard ratio (HR) of 1.26 per quartile increase (95% CI, 1.09 –1.45). Presence of steatosis on baseline biopsy was associated with an increased outcome rate among patients with bridging fibrosis (P < .0001) and a decreased rate among patients with cirrhosis (P = .006). Presence of Mallory bodies was associated with outcomes (HR, 1.59; 95% CI, 1.10 –2.31) as was significant weight change of ≥5% in the first year after randomization (HR, 1.25 per category increase in weight, 95% CI, 1.01–1.55). CONCLUSIONS Insulin resistance, histologic features of fatty liver disease, and weight change were associated with outcomes of chronic hepatitis C. Improvement in these weight-related factors might modify disease progression.

BACKGROUND & AIMS The incidence of liver disease progression among subjects with histologically advanced but compensated, chronic hepatitis C is incomplete. METHODS The Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial was a randomized study of 3.5 years of maintenance peginterferon treatment on liver disease progression among patients who had not cleared virus on peginterferon and ribavirin therapy. Patients were followed subsequently off therapy. Because maintenance peginterferon treatment did not alter liver disease progression, we analyzed treated and control patients together. Among 1,050 subjects (60% advanced fibrosis, 40% cirrhosis), we determined the rate of progression to cirrhosis over 4 years and of clinical outcomes over 8 years. RESULTS Among patients with fibrosis, the incidence of cirrhosis was 9.9% per year. 679 clinical outcomes occurred among 329 subjects. Initial clinical outcomes occurred more frequently among subjects with cirrhosis (7.5%/year) than with fibrosis (3.3%/year) (P <0.0001). Child-Turcotte-Pugh (CTP) ≥7 was the most common first outcome, followed by hepatocellular carcinoma. Following occurrence of a score CTP ≥7, the rate of subsequent events increased to 12.9%/year, including a death rate of 10%/year. Age and sex did not influence outcome rates. Baseline platelet count was a strong predictor of all clinical outcomes. During the 8 years of follow-up, death or liver transplantation occurred among 12.2% of patients with advanced fibrosis and 31.5% of those with cirrhosis. CONCLUSIONS Among patients with advanced hepatitis C who failed peginterferon and ribavirin, the rate of liver-related outcomes, including death and liver transplantation, is high, especially once CTP reaches at least 7.

Introduction The uptake of HIV testing and linkage to care remains low among men, contributing to high HIV incidence in women in South Africa. We conducted the “Home‐Based Intervention to Test and Start” (HITS) in a 2x2 factorial cluster randomized controlled trial in one of the World’s largest ongoing HIV cohorts in rural South Africa aimed at enhancing both intrinsic and extrinsic motivations for HIV testing. Methods Between February and December 2018, in the uMkhanyakude district of KwaZulu‐Natal, we randomly assigned 45 communities (clusters) (n = 13,838 residents) to one of the four arms: (i) financial incentives for home‐based HIV testing and linkage to care (R50 [$3] food voucher each); (ii) male‐targeted HIV‐specific decision support application, called EPIC‐HIV; (iii) both financial incentives and male‐targeted HIV‐specific decision support application and (iv) standard of care (SoC). EPIC‐HIV was developed to encourage and serve as an intrinsic motivator for HIV testing and linkage to care, and individually offered to men via a tablet device. Financial incentives were offered to both men and women. Here we report the effect of the interventions on uptake of home‐based HIV testing among men. Intention‐to‐treat (ITT) analysis was performed using modified Poisson regression with adjustment for clustering of standard errors at the cluster levels. Results Among all 13,838 men ≥ 15 years living in the 45 communities, the overall population coverage during a single round of home‐based HIV testing was 20.7%. The uptake of HIV testing was 27.5% (683/2481) in the financial incentives arm, 17.1% (433/2534) in the EPIC‐HIV arm, 26.8% (568/2120) in the arm receiving both interventions and 17.8% in the SoC arm. The probability of HIV testing increased substantially by 55% in the financial incentives arm (risk ratio (RR)=1.55, 95% CI: 1.31 to 1.82, p < 0.001) and 51% in the arm receiving both interventions (RR = 1.51, 95% CI: 1.21 to 1.87 p < 0.001), compared to men in the SoC arm. The probability of HIV testing did not significantly differ in the EPIC‐HIV arm (RR = 0.96, 95% CI: 0.76 to 1.20, p = 0.70). Conclusions The provision of a small financial incentive acted as a powerful extrinsic motivator substantially increasing the uptake of home‐based HIV testing among men in rural South Africa. In contrast, the counselling and testing application which was designed to encourage and serve as an intrinsic motivator to test for HIV did not increase the uptake of home‐based testing.