Meng-Hsuan Hsieh

Baseline gamma-glutamyl transferase levels strongly correlate with hepatocellular carcinoma development in non-cirrhotic patients with successful hepatitis C virus eradication

BACKGROUND & AIMS Hepatitis C virus (HCV)-infected patients with cirrhosis remain at risk of hepatocellular carcinoma (HCC) even after achieving sustained virological response (SVR). The aim of the study was to explore the incidence and risk for HCC among non-cirrhotic patients with an SVR. METHODS A total of 642 patients with an SVR after peginterferon/ribavirin therapy were enrolled with a median follow-up period of 53.0 months (range: 6-133 months). RESULTS Thirty-three of the 642 (5.1%) patients developed HCC over 2324.8 person-years of follow-up. Cox regression analysis revealed that the strongest predictive factor of HCC occurrence was liver cirrhosis (HR 4.98, 95% CI 2.32-10.71, p<0.001), followed by age (HR 1.06, 95% CI 1.02-1.11, p=0.005) and γGT levels (HR 1.008, 95% CI 1.004-1.013, p<0.001). The incidence of HCC did not differ between patients with high and low baseline γGT levels among patients with cirrhosis (p=0.53), but the incidence of HCC was significantly higher in non-cirrhotic patients with high γGT levels compared with those with low γGT levels (p=0.001). Cox regression analysis revealed that the strongest factors associated with HCC development in non-cirrhotic sustained responders were baseline γGT levels (HR 6.44, 95% CI 2.20-18.89, p=0.001) and age (HR 3.68, 95% CI 1.33-10.17, p=0.012). The incidence of HCC was not different between older non-cirrhotic patients with high γGT levels and cirrhotic patients (p=0.34). CONCLUSIONS HCC remains a threat in non-cirrhotic patients with an SVR. Serum γGT levels helped to identify potential patients at high risk.

Huge gap between clinical efficacy and community effectiveness in the treatment of chronic hepatitis C: a nationwide survey in Taiwan.

AbstractPeginterferon/ribavirin provides a substantially high treatment efficacy for chronic hepatitis C virus (HCV) infections in Asians. Whether the clinical efficacy can be translated to community effectiveness remains unclear.The disease awareness, treatment accessibility, recommendations, acceptance, and barriers to anti-HCV treatment were explored to clarify the issue with a 3-step nationwide investigation in Taiwan. A crude HCV-infected population was estimated using databases from 3 large-scale surveillance studies and age-/geographic-specific population database. HCV awareness and accessibility were investigated at the patient level in 58,129 residents. The recommendations/acceptances and barriers to treatment at the provider level were evaluated using a prospective, nationwide approach to 89 gastroenterologists/hepatologists.The estimated 10-year interval age-adjusted anti-HCV-seropositive population is 745,109 (3.28%), with an anticipated HCV-viremic population of 554,361. Of anti-HCV-seropositive subjects, 36.2% had disease awareness. Among those with awareness, 39.6% had accessibility. The recommendation/acceptance rate of antiviral therapy was 70.6%. The treatment rate was 10.1% and 13.7% for the anti-HCV-seropositive and HCV-viremic population, respectively. With an anticipated treatment success rate of 80% in Taiwan, 8.1% of the anti-HCV-seropositive and 10.9% of the HCV-viremic population achieved successful treatment. The major treatment barriers were fear of adverse effects (37%), major disorders (17.6%), ineligibility for insurance reimbursement (17.6%), and lack of therapy awareness (11.3%).Despite the high rates of treatment response and nationwide coverage of insurance reimbursement, there remains a large gap between clinical efficacy and community effectiveness in anti-HCV treatment in Taiwan. Increasing disease awareness/treatment accessibility and introducing new therapeutic strategies with high tolerability are warranted.

Hepatitis C virus infection and metabolic syndrome - a community-based study in an endemic area of Taiwan.

Metabolic syndrome (MS) is a complicated disorder associated with a high risk of future development of micro‐ and macrovascular complications. The extrahepatic manifestations of hepatitis C virus (HCV) infection can include multiple metabolic abnormalities. However, the extent, severity, and characteristics of MS in HCV‐infected patients have rarely been investigated in community‐based settings. This study aimed to determine the difference in prevalence and distribution of the components of MS between HCV‐infected patients and healthy controls. Multipurpose mass screening of adults was conducted in an HCV‐endemic area of Southern Taiwan. Clinical profiles in terms of anthropometric data and MS components, as well as viral hepatitis markers, were assessed. Two hundred and thirty‐seven adults (94 males; mean age, 55.5 ± 10.8 years) were recruited. The prevalence of anti‐HCV seropositivity was 39.2% (93/237). The prevalence of MS was higher in the HCV‐infected individuals (24.7%, 23/93) than in the control, uninfected subjects (13.2%, 19/144, p = 0.02). In terms of MS components, HCV‐infected subjects had a higher prevalence of high waist circumference (51.6% vs. 25.7%, p < 0.001) and hypertension (58.1% vs. 36.8%, p = 0.001) than controls. Multivariate logistic regression analysis demonstrated that anti‐HCV positivity was significantly associated with MS (odds ratio, 6.4; 95% confidence interval, 1.82–22.84; p = 0.004). HCV infection was associated with a higher prevalence of MS. Determination of MS in patients with HCV infection could therefore be indicated.

Reactivation of hepatitis B in patients of chronic hepatitis C with hepatitis B virus infection treated with direct acting antivirals

Hepatitis B virus (HBV) may reactivate when treating chronic hepatitis C (CHC) with direct acting antivirals (DAA). We aim to investigate the risk of HBV reactivation during DAA therapy.

Association of diabetes and PNPLA3 genetic variants with disease severity of patients with chronic hepatitis C virus infection.

BACKGROUND & AIMS Genetic variants of patatin-like phospholipase domain-containing 3 (PNPLA3) and diabetes are associated with liver disease severity, in patients with chronic hepatitis C (CHC) infection. We aimed at exploring their interaction in determining hepatitis C virus (HCV)-related liver fibrosis. METHODS The PNPLA3 genetic polymorphism at rs738409 was verified in 1077 biopsy-proven CHC patients. Other clinical variables, including diabetes status, were analysed for factors associated with bridging fibrosis. RESULTS Patients with advanced liver fibrosis had higher proportions of the GG genotype (14.5% vs. 10.4%, p=0.06 in recessive model) and GG/GC genotype carriage (64.0% vs. 56.8%, p=0.03 in dominant model). Stepwise logistic regression analysis revealed that factors predictive of advanced liver fibrosis included age (odds ratio [OR]: 1.02, 95% confidence intervals [CI]: 1.008-1.037, p=0.002), diabetes (OR: 1.81, CI: 1.236-2.653, p=0.002), α-fetoprotein (OR: 1.006, CI: 1.001-1.01, p=0.01), platelet counts (OR: 1.009, CI: 1.006-1.012, p<0.001), and PNPLA3 rs738409 CG/GG genotype (OR: 1.34, CI: 1.006-1.785, p=0.046). When patients were grouped according to their diabetes status, the PNPLA3 genetic variants were associated with advanced liver fibrosis in diabetic patients only, but not in non-diabetic patients. The PNPLA3 gene was the most important predictive factor of bridging fibrosis in diabetic patients, using the recessive model (OR: 4.53, CI: 1.356-15.106, p=0.014) or the dominant model (OR: 2.20, CI: 1.026-4.734, p=0.04). Compared to non-diabetic patients, patients with the diabetes/GG genotype were more likely to have advanced liver fibrosis (OR: 8.79, CI: 2.889-26.719, p<0.001), followed by those with diabetes/non-GG genotype (OR: 1.55, CI: 1.048-2.286, p=0.03). CONCLUSIONS The effect of PNPLA3 genetic variants in HCV-related advanced liver fibrosis was enhanced in diabetic patients. The strong genetic-environmental interaction contributed to the high risk of advanced liver disease in CHC patients.

The outcomes of glucose abnormalities in pre-diabetic chronic hepatitis C patients receiving peginterferon plus ribavirin therapy.

Pre‐diabetes is a risk factor for type 2 diabetes mellitus (DM) development. This study aimed to elucidate the impact of treatment response on sequential changes in glucose abnormalities in pre‐diabetic chronic hepatitis C (CHC) patients.

Hepatitis C Virus Infection among Injection Drug Users with and without Human Immunodeficiency Virus Co-Infection

The aim of this study is to explore the prevalence of hepatitis C virus (HCV) infection among injection drug users (IDUs) with and without human immunodeficiency virus (HIV) infection in southern Taiwan. For 562 IDUs (265 anti-HIV negative, 297 anti-HIV positive), we analyzed liver function, anti-HIV antibody, anti-HCV antibody, HCV viral loads, and hepatitis B surface antigen (HBsAg). HIV RNA viral loads and CD4 cell count for anti-HIV-seropositive IDUs and the HCV genotype for HCV RNA-seropositive IDUs were measured. The seroprevalence rates of anti-HIV, anti-HCV, and HBsAg were 52.8%, 91.3%, and 15.3%, respectively. All the anti-HIV-seropositive IDUs were positive for HIV RNA. Anti-HCV seropositivity was the most important factor associated with HIV infection (odds ratio [OR], 25.06; 95% confidence intervals [CI], 8.97–74.9), followed by male gender (OR, 6.12; 95% CI, 4.05–9.39) and HBsAg seropositivity (OR, 1.90; 95% CI, 1.11–3.34). Among IDUs positive for anti-HCV, 80.7% had detectable HCV RNA. HCV viremia after HCV exposure was strongly related to HIV infection (OR, 6.262; 95% CI, 1.515–18.28), but negatively correlated to HBsAg seropositivity (OR, 0.161; 95% CI, 0.082–0.317). HCV genotype 6 was the most prevalent genotype among all IDUs (41.0%), followed by genotypes 1 (32.3%), 3 (12.8%), and 2 (5.6%). In conclusion, about half IDUs were infected with HIV and >90% with HCV infection. Male and seropositivity for HBsAg and anti-HCV were factors related to HIV infection among our IDUs. HIV was positively correlated, whereas hepatitis B co-infection was negatively correlated with HCV viremia among IDUs with HCV exposure. Different HCV molecular epidemiology was noted among IDUs.

LACK OF ASSOCIATIONS BETWEEN SEVERAL POLYMORPHISMS IN CYTOKINE GENES AND THE RISK OF CHRONIC OBSTRUCTIVE PULMONARY DISEASES IN TAIWAN

Cytokine‐induced inflammation is the predominant underlying mechanism in chronic obstructive pulmonary disease (COPD). Genetic factors may play a pivotal role in the development of this disease. This study looked at the relationship between COPD and genetic polymorphisms in the genes encoding some of these cytokines in a Taiwanese population. The genetic polymorphisms examined in this study were tumor necrosis factor (TNF)‐α(−308), TNF‐α(+489), interleukin(IL)‐1β(−31), interleukin‐1 receptor antagonist (IL‐1 RN), and IL‐6(−174). In total, 30 patients with COPD, 64 subjects at risk of COPD and 115 controls were recruited to the study between 1999 and 2003. DNA was collected from these subjects and analyzed by polymerase chain reaction with sequence‐specific primers and restriction enzyme fragment length polymorphism analysis. The frequencies of cytokine genotypes in COPD cases and controls, respectively, were as follows: for G/G in TNF‐α(−308), 76.7% and 83.5%; for G/G in TNF‐α(+ 489), 76.7% and 68.7%; for C/T in IL‐1β(−31), 60.0% and 55.7%; for 4R/4R in IL‐1 RN, 80.0% and 86.1%; and for G/G in IL‐6(−174), 100.1% and 98.3%. There was no difference in the distribution of the frequencies of these genotypes and alleles between COPD cases and controls. Moreover, no association was found between these genetic polymorphisms in cytokines and COPD (regardless of COPD subtypes) with respect to cigarette smoking or pulmonary function tests. Despite this, smoking is still an important risk factor for developing COPD.

Clinical utility of host genetic IL‐28B variants in hepatitis C virus genotype 1 Asian patients retreated with pegylated interferon plus ribavirin

Host interleukin‐28B (IL‐28B) genetic variants determine a sustained virological response (SVR) in hepatitis C virus genotype 1 (HCV‐1) treatment‐naïve patients. Its impact on treatment‐experienced Asian patients with peginterferon/ribavirin in is to be elucidated.

Performance characteristics of a combined hepatitis C virus core antigen and anti–hepatitis C virus antibody test in different patient groups

We evaluated the performance of a hepatitis C virus (HCV) antigen/antibody combination test [Murex HCV Antigen/Antibody Combination Test (Murex Ag/Ab test)] by comparing it with the current third‐generation HCV antibody enzyme immunoassay (anti‐HCV). A total of 403 serum samples were consecutively collected from four patient groups: healthy controls (n = 100); HCV‐infected patients (HCV group, n = 102); Human immunodeficiency virus (HIV)/HCV‐infected patients (HIV/HCV group, n = 100); and patients with uremia (uremia group, n = 101). Performances were evaluated for the Murex Ag/Ab, anti‐HCV, and HCV RNA in the HIV/HCV and uremia patient groups. In the HCV group, all 102 samples showed concordant positive and negative results for anti‐HCV, Murex Ag/Ab, and HCV RNA tests. In the HIV/HCV group, all 100 samples were positive for both anti‐HCV and Murex Ag/Ab tests, whereas 88 patients (88%) were HCV RNA positive. In the uremia group, 14 (69.0%) of the 23 anti‐HCV‐positive patients were HCV RNA positive, whereas 14 (77.8%) of the 18 Murex Ag/Ab–positive patients were HCV RNA positive. None of anti‐HCV‐negative or Murex Ag/Ab–negative patients were HCV RNA positive. Based on the HCV RNA assay, the sensitivities for both anti‐HCV and Murex Ag/Ab assays were 100%, whereas the specificities of these two assays were 89.7% and 95.4%, respectively. With good sensitivity and specificity, the Murex Ag/Ab assay could be a useful alternative diagnostic tool, especially in immunocompromised populations, such as patients with uremia or those infected with HIV.