Suna Yapali

Serum levels of adipokines in patients with chronic HCV infection: relationship with steatosis and fibrosis.

BACKGROUND AND AIMSnHepatic steatosis and fibrosis are common histological findings in patients with chronic hepatitis C virus (HCV) infection. In this study we sought to determine whether serum levels of three adipokines (leptin, adiponectin and resistin) show any biochemical correlation with hepatic steatosis and fibrosis in patients with chronic HCV infection.nnnMETHODSnWe examined a total of 51 patients with chronic HCV infection (22 males and 29 females, mean BMI: 27.4+/-5kg/m(2)) and 24 healthy control subjects (10 males and 14 females, mean BMI: 23.2+/-3kg/m(2)). Liver steatosis and fibrosis were scored on biopsies. Serum levels of leptin, adiponectin and resistin were determined by ELISA.nnnRESULTSnHCV genotypes were 1b in 41 patients (80.4%), 3a in three patients (5.9%), 2a in two patients (3.9%), 1a in two patients (3.9%), 1c in one patient (2%), and 2b in one patient (2%). Serum levels of leptin, resistin, and the leptin-to-adiponectin ratio were significantly higher in patients with chronic HCV infection than in controls. Steatosis and fibrosis were detected in 33.3% and 70.5% of chronic HCV patients, respectively. No significant association with serum adipokine levels and degree of steatosis was evident. Low serum levels of resistin were associated with the presence of fibrosis independently of potential confounders.nnnCONCLUSIONSnPatients with chronic HCV infection display elevated levels of adipokines in their sera. Reduced concentrations of resistin may be a biochemical marker of fibrosis in this patient group.

Systematic review: identifying patients with chronic hepatitis C in need of early treatment and intensive monitoring – predictors and predictive models of disease progression

Advances in hepatitis C therapies have led to increasing numbers of patients seeking treatment. As a result, logistical and financial concerns regarding how treatment can be provided to all patients with chronic hepatitis C (CHC) have emerged.

Outcomes of Patients With Chronic Hepatitis B Who Do Not Meet Criteria for Antiviral Treatment at Presentation

BACKGROUND & AIMSnThe availability of potent, well-tolerated, oral antivirals with low rates of resistance has led many experts to recommend liberalizing indications for the treatment of chronic hepatitis B (CHB). This study sought to determine the rate of transitions to an active phase of infection, the frequency of treatment initiation, and the clinical outcomes of patients with CHB who did not meet treatment criteria at presentation.nnnMETHODSnWe reviewed medical records of patients with CHB, seen in the liver clinics at the University of Michigan Health System from 1999 through 2010, who did not receive antiviral treatment within 6 months of presentation. We collected data on transitions between different phases of CHB, hepatitis B e antigen (HBeAg) seroconversion, loss of hepatitis B surface antigen (HBsAg), and the development of hepatocellular carcinoma (HCC). Data analyses were censored or truncated at the time of treatment initiation or development of an outcome.nnnRESULTSnOf the 234 patients analyzed, 52.1% were men (median age, 35 y), 72.2% were Asian, and 81.2% were HBeAg-negative. During a median follow-up period of 51 months, 19.2% of patients transitioned to a more active disease phase and 18.8% started antiviral therapy. Of the 44 HBeAg-positive patients, 4 patients (9%) had spontaneous HBeAg seroconversion. Nine HBeAg-negative patients but none of the HBeAg-positive patients lost HBsAg. The cumulative probability of HBsAg loss among HBeAg-negative patients was 1% at year 5 and 21% by year 10. No patients had flares of icteric hepatitis or hepatic decompensation. None of the HBeAg-positive patients developed HCC, whereas 2 HBeAg-negative patients developed HCC.nnnCONCLUSIONSnCareful monitoring of patients with CHB who did not meet treatment criteria at presentation permits timely initiation of treatment, with a low risk of adverse clinical outcomes, based on a retrospective study with a median follow-up period of 4.3 years. These findings indicate that current guidelines for initiating treatment are appropriate.

Potential Benefit of Telbivudine on Renal Function Does Not Outweigh Its High Rate of Antiviral Drug Resistance and Other Adverse Effects

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Admissions for hepatitis B reactivation in patients receiving immunosuppressive therapy remain unchanged from 1999 to 2014

AbstractBackgroundReactivation of hepatitis B virus (HBV) replication in patients with chronic or past HBV infection receiving immunosuppressive therapy (IST) can be prevented through HBV screening and prophylactic antiviral therapy. We aimed to determine the occurrence of severe HBV reactivation secondary to IST in the era of HBV nucleos/tide analogs, the implicated IST, and outcomes.nMethodsWe conducted a retrospective chart review of adult patients who were HBsAg+ and HBV DNA+ and had received IST within 90xa0days of admission to our hospital.ResultsOf 1446 patients with HBV diagnosis code admitted from 1999 to 2014, 17 had HBV reactivation, 8 of whom were admitted after 2009. Nine patients had hematologic conditions, three solid organ transplants, one hepatocellular carcinoma, and four other nonmalignant diseases. Implicated IST included chemotherapy, prednisone, antirejection therapies, budesonide, and a JAK-2 inhibitor. Three patients were screened for HBV prior to IST, but none was given antiviral prophylaxis. Six patients were initially admitted to other facilities, only two were tested for HBV, and one was started on antiviral therapy prior to transfer. At admission to our hospital, all 17 were HBsAg+ and HBV DNA+. Despite antiviral therapy, five patients decompensated, three died, and two had a liver transplant.ConclusionSevere HBV reactivation requiring hospital admission continues to occur because HBV screening was not performed and a prophylactic antiviral not given to those who tested positive. HBV reactivation can occur in a variety of clinical settings and in association with drugs not considered to be highly immunosuppressive.

Changes in characteristics of hepatitis C patients seen in a liver centre in the United States during the last decade.

With the approval of 2 direct‐acting antivirals (DAAs) in 2011 and anticipation of interferon (IFN)‐free regimens, more hepatitis C virus (HCV) chronically infected patients are now seeking treatment. To describe the characteristics of newly referred HCV patients in 2011–2012 (Era‐2) and compare them to those seen in 1998–1999 (Era‐1). Retrospective data were collected from HCV patients newly referred to our tertiary liver clinics. Advanced liver disease was defined as cirrhosis (based on histology or Aspartate aminotransferase–platelet‐ratio index (APRI) >2), hepatic decompensation or hepatocellular carcinoma (HCC). A total of 1348 patients (538 in Era‐1, 810 in Era‐2) were included. Compared to Era‐1, Era‐2 patients were older (median age 56 vs 45 years), more likely to be black (17.2% vs 11.6%) and had a longer interval between diagnosis and referral (median 4 vs 2 years). Genotype (GT) 1 predominated in both Eras with a significant increase in GT1a from 39.9% in Era‐1 to 53.8% in Era‐2. A higher per cent of patients in Era‐2 were treatment experienced, but 77% had never received treatment. Era‐2 patients were more likely to have advanced disease at referral (61.6% vs 51.5%, P < 0.001), with an eightfold higher prevalence of HCC (21.6% vs 2.6%, P < 0.001). HCV patients newly referred in recent years were older, predominantly infected with GT1a and had more advanced liver disease yet only a quarter had received HCV treatment. Reduction in HCV disease burden will require development of treatment regimens targeted towards patients in the current Era as well as increase in diagnosis and referral of patients for treatment.

Does suppression of HBV replication by antiviral therapy confer the same benefit as host immune control of HBV

Approximately 50% of hepatocellular carcinoma (HCC) worldwide is attributed to chronic HBV infection.1 Data from the population-based Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-HBV REVEAL-HBV study showed that high levels of serum HBV DNA are associated with increased risk of cirrhosis, HCC and liver-related mortality.2 The REVEAL-HBV study also demonstrated that among hepatitis B surface antigen positive persons with high levels of HBV DNA at enrolment, the risk of HCC was lower in those who had decline in HBV DNA levels during follow-up compared with those with persistently high levels of HBV DNA. These data suggest that antiviral therapy may decrease the risk of HCC through suppression of HBV replication.nnThere has been only one randomised controlled trial of nucleos(t)ide analogue (NUC) treatment in patients with chronic hepatitis B (CHB) with HCC as one of the predefined outcomes.3 This study comparing lamivudine versus placebo was terminated after a median of 32.4u2005months (range 1–42 months) because a significant difference in the composite outcome of disease progression which included HCC was observed between the two groups. At the time of study termination, HCC had occurred in 3.9% of the lamivudine-treated group and 7.4% of the placebo group with a HR of 0.49, and 95% CI 0.25 to 0.99 (p=0.047); however, this difference was no longer significant when the five cases of HCC diagnosed during the 1st year were excluded (p=0.052). …

Should treatment of hepatitis B patients be based solely on liver fibrosis

he ultimate goal of hepatitis B treatment is to prevent Tprogression to cirrhosis, liver failure, and hepatocellular carcinoma (HCC). This goal can be achieved with sustained suppression of hepatitis B virus (HBV) replication and hepatic inflammation. Current treatment guidelines for hepatitis B recommend antiviral therapy for patients with active or advanced liver disease and high serum HBV DNA levels. For patients who do not have cirrhosis, these guidelines recommend that the decision to start treatment or to monitor should be based not only on the stage of liver fibrosis but also on the activity of liver disease and the predicted risk of cirrhosis and HCC. Unlike hepatitis C (HCV) where the vast majority of HCC cases occur in patients with cirrhosis, 3%–47% of HBVrelated HCC occurs in the absence of cirrhosis. One major difference between HBV and HCV is that HBV is a DNA virus, and HBV DNA can be integrated into the host genome and may have direct oncogenic effect through activation of oncogenic pathways or down-regulation of tumor suppressor pathways. Furthermore, ample evidence mainly generated from the population-based Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus study shows that high levels of serum HBV DNA are associated with increased risk of cirrhosis, HCC, and liverrelated mortality. Professional society guidelines agree that treatment should be initiated in non-cirrhotic patients with serum HBV DNA >20,000 IU/mL and alanine aminotransferase (ALT) levels higher than 2 times upper limit of normal (ULN) or histologic evidence of moderate-to-severe inflammation or fibrosis. The cutoff values of ALT, HBV DNA, and the need for liver biopsy in determining treatment indications vary slightly among the guidelines. Because HBV DNA levels are generally lower in hepatitis B e antigen (HBeAg)–negative patients, cutoff values for initiating treatment in HBeAg-negative patients are lower than in HBeAg-positive patients. Recognizing that liver biopsy is not performed on all patients with chronic hepatitis B, the guidelines of the American Association for the Study of Liver Diseases (AASLD) and the Asian Pacific Association for the Study of the Liver (APASL) primarily rely on ALT levels to guide treatment decisions. For HBeAg-negative patients with HBV DNA 2000–20,000 IU/mL, the AASLD and APASL guidelines recommend treatment for patients with ALT levels higher than 2 times ULN and liver biopsy to guide treatment decisions for patients with ALT level 1–2 times ULN, particularly if they are older than the age of 40. United States Panel Algorithm (USPA) recommends liver biopsy in patients older than age 35–40 who have serum HBV DNA 2000 IU/mL and normal ALT levels. USPA and AASLD suggest using the updated ULN for ALT, 30 U/L for men and 19 U/L for women, whereas the European Association for the Study of the Liver (EASL) and APASL suggest the traditional definition of ULN for ALT (40 U/L). The EASL guidelines place more emphasis on liver histology; they recommend treatment of patients with ALT above ULN if liver biopsy shows at least a metavir activity grade of A2

Epidemiology and viral risk factors for hepatocellular carcinoma in the Eastern Mediterranean countries

Given the high prevalence of viral hepatitis in the Eastern Mediterranean countries, hepatitis B and C infections are the major causes of hepatocellular carcinoma (HCC) in the region. Most cases are associated with cirrhosis related to hepatitis B or C infection. Environmental, host genetic and viral factors can affect the risk of HCC in patients with hepatitis B and C infection. Understanding the epidemiology and viral risk factors in the region provides the implementation of strategies for prevention and treatment of viral hepatitis. Herein, we reviewed the epidemiology, burden of disease and viral risk factors for HCC.