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Hepatite B

Factors That Predict Response of Patients With Hepatitis B e Antigen–Positive Chronic Hepatitis B to Peginterferon-Alfa.
Therapy with pegylated interferon (PEG-IFN)–alfa results in sustained response in a minority of patients with chronic hepatitis B virus (HBV) infection and has considerable side effects. We analyzed data from the 2 largest global trials of hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B to determine which are most likely to respond to PEG-IFN–alfa therapy.The study included 542 patients treated with PEG-IFN–alfa-2a (180 µg/wk, 48 wk) and 266 patients treated with PEG-IFN–alfa-2b (100 µg/wk, 52 wk). Eighty-seven patients were excluded, leaving 721 patients for analysis. A sustained response was defined as HBeAg loss and HBV-DNA level less than 2.0 × 103 IU/mL 6 months after treatment. Logistic regression analysis was used to identify predictors of sustained response and a multivariable model was constructed. HBV genotype, high levels of alanine aminotransferase (ALT; =2 × upper limit of normal), low levels of HBV DNA (<2.0 × 108 IU/mL), female sex, older age, and absence of previous IFN therapy predicted a sustained response. Genotype A patients with high ALT and/or low HBV-DNA levels had a high predicted probability (>30%) of a sustained response. The strongest predictors of response were a high level of ALT in genotype B patients and a low level of HBV DNA in genotype C patients. Genotype D patients had a low chance of sustained response, irrespective of ALT or HBV-DNA levels. The best candidates for a sustained response to PEG-IFN–alfa are genotype A patients with high levels of ALT or low levels of HBV DNA, and genotypes B and C patients who have both high levels of ALT and low HBV DNA. Genotype D patients have a low chance of sustained response. (GASTROENTEROLOGY 2009; 137:2002-2009).


Hepatite C

Treatment of insulin resistance with metformin in naďve genotype 1 chronic hepatitis C patients receiving peginterferon alfa-2a plus ribavirin.
Insulin resistance affects sustained virological response (SVR) in chronic hepatitis C. To know whether adding metformin to standard antiviral treatment improves SVR, we conducted a prospective, multicentered, randomized, double-blinded, placebo-controlled trial in 19 Spanish hospitals, including 123 consecutive patients with genotype 1 chronic hepatitis C and insulin resistance. Patients were randomized to receive either metformin (arm A; n = 59) or placebo (arm B; n = 64) in addition to peginterferon alfa-2a (180 g/week) and ribavirin (1000-1200 mg/day). The primary end point was SVR, and secondary endpoints were viral clearance at weeks 12, 24, and 48, and changes in the homeostasis model assessment (HOMA) index over the first 24 weeks. There were no differences between arms at baseline. In the intent-to-treat analysis, SVR was observed in 53% versus 42% in arm A and arm B, respectively (P = NS). In the subgroup analyses, SVR was higher in females (n = 54) receiving metformin: arm A, 58% (15/26) versus 29% (8/28) arm B (P = 0.03). In the per protocol analysis (PPA; n = 101), SVR was 67% in arm A and 49% in arm B (P = 0.06). Viral decline during the first 12 weeks was greater in females receiving metformin: -4.88 (1.18) versus -4.0 (1.44) (P = 0.021), whereas no differences were seen in males. The triple therapy was well tolerated, but diarrhea was more often seen in arm A (34% versus 11%; P < 0.05). Conclusion: Adding metformin to peginterferon and ribavirin was safe and improved insulin sensitivity. Although the study failed to show a statistically significant difference between arms, it did show an improved SVR in females. (HEPATOLOGY 2009; 50:1702-1708).

Public health impact of antiviral therapy for hepatitis C in the United States.
Despite dramatic improvements in antiviral therapy for hepatitis C, there is reason to believe that the uptake of antiviral therapy remains limited. The aims of this study were to determine the number of patients being treated with antiviral therapy in the U.S., to estimate the public health impact of these treatment patterns, and to identify barriers to treatment for patients with hepatitis C. Data on the number of new patient pegylated interferon prescriptions each year, from 2002-2007, was obtained from Wolters Kluwer Inc., which maintains an electronic audit of pharmacies nationwide. A Markov model was created of the population with chronic hepatitis C in the U.S. from 2002 to 2030, and was used to estimate the number of liver-related deaths caused by hepatitis C that will be prevented by current treatment patterns. The National Health and Nutrition Evaluation Survey (NHANES) Hepatitis C Follow-Up Questionnaire was used to investigate reasons for lack of treatment and to identify strategies for improving access. Approximately 663,000 patients received antiviral therapy between 2002 and 2007, and treatment rates appear to be declining. If this trend continues, only 14.5% of liver-related deaths caused by hepatitis C from 2002-2030 will be prevented by antiviral therapy. Results from the NHANES questionnaire suggest that the primary barrier to treatment is lack of diagnosis, with 69/133 (adjusted proportion 49%) of respondents previously unaware that they had hepatitis C. Conclusion: Efforts to improve rates of diagnosis and treatment will be required if the future public health burden of hepatitis C is to be ameliorated. (HEPATOLOGY 2009; 50:1750-1755).


Esteatose Hepática

Validity of real time ultrasound in the diagnosis of hepatic steatosis: A prospective study.
Ultrasound is used to screen for hepatic steatosis, the most common liver disease in the United States. However, few studies have prospectively evaluated the accuracy of ultrasound to diagnose hepatic steatosis. Therefore, a double blinded prospective study was performed in consecutive patients undergoing liver biopsy to evaluate the accuracy of ultrasound to diagnose hepatic steatosis. Real time ultrasound was performed just prior to the biopsy by a single investigator masked to the clinical diagnosis. The liver biopsy was reviewed by a pathologist masked to the clinical indication or sonographic findings. Of 73 consecutive patients studied, macrovesicular steatosis of any severity on biopsy was found in 46 (63%) and micro vesicular fat found in 51 (69.9%). The overall impression of the sonographer for the presence of macrovesicular hepatic steatosis of any degree had a sensitivity of 60.9% and a specificity of 100%. The sensitivity increased to 100% and the specificity to 90% when there was20% of fat. The zonular distribution of the fat did not alter the diagnostic accuracy of ultrasound. Ultrasound had a poor yield in the diagnosis of microvesicular fat with an overall sensitivity of 43% and a specificity of 73%. The combination of increased echogenicity and portal vein blurring on ultrasound had the greatest sensitivity in the diagnosis of hepatic steatosis. Real time ultrasound using a combination of sonographic findings has a high specificity but underestimates the prevalence of hepatic steatosis when there is<20% fat. (JOURNAL OF HEPATOLOGY 2009; 51:1061-1067).


Carcinoma Hepatocelular

Transarterial chemotherapy alone versus transarterial chemoembolization for hepatocellular carcinoma: A randomized phase III trial.
Patients with newly diagnosed unresectable HCC were randomly assigned to either a TACE group or a TAI group. Zinostatin stimalamer was injected into the hepatic artery, together with gelatin sponge in the TACE group and without gelatin sponge in the TAI group. Treatment was repeated when follow-up computed tomography showed the appearance of new lesions in the liver or re-growth of previously treated tumors. Seventy-nine patients were assigned to the TACE group, and 82 were assigned to the TAI group. The two groups were comparable with respect to their baseline characteristics. At the time of the analysis, 51 patients in the TACE group and 58 in the TAI group had died. The median overall survival time was 646days in the TACE group and 679days in the TAI group (p=0.383). The results of this study suggest that treatment intensification by adding embolization did not increase survival over TAI with zinostatin stimalamer alone in patients with HCC. (JOURNAL OF HEPATOLOGY 2009; 51:1030-139).

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