Baseline risk factors for relapse in HIV/HCV co-infected patients treated with PEG-IFN/RBV

Purpose

Hepatitis C virus (HCV) viral relapse (VR) after end-of-treatment response (ETR) in human immunodeficiency virus (HIV) co-infected patients is observed in as many as one in three co-infected patients. The aim of the study was to identify baseline risk factors for VR in HIV/HCV co-infected patients treated with pegylated interferon plus ribavirin (PEG-INF/RBV).

Methods

A total of 212 Caucasian HIV-infected patients with chronic hepatitis C naïve for PEG-INF/RBV were followed prospectively. Patients were included in this prospective study if they had completed a full course of therapy with an ETR. We assessed the relationship between VR rate and potential predictors of relapse.

Results

Of the patients followed, 130 (61.3 %) attained ETR and 103 (79.2 %) achieved sustained virological response (SVR). Consequently, 27 (20.8 %) showed VR. Patients who relapsed were more often male (p = 0.036), carried the non-CC rs14158 genotype in the low-density lipoprotein receptor (LDLr) gene (p = 0.039), had higher baseline HCV RNA levels (p = 0.012), body mass index (BMI) ≥25 kg/m² (p = 0.034), significant liver fibrosis (p < 0.001), had been diagnosed with acquired immunodeficiency syndrome (AIDS)-defining criteria in the past (p = 0.001) and bore the HCV genotypes 1/4 (p = 0.046) when compared with SVR patients. The IL28B genotype was not associated with relapse. Multivariate binary logistic regression showed that high baseline HCV RNA, significant liver fibrosis, HCV genotypes 1/4, being overweight and being diagnosed with AIDS-defining criteria in the past were independently associated with relapse.

Conclusions

Our study shows that VR can be accurately predicted in HIV/HCV co-infected patients on the basis of risk factors which can be identified before treatment.     

Incidence and predictors of hematological side effects in chronic HCV Egyptian patients treated with PEGylated interferon and ribavirin

Aim

The aim of this paper was to study the incidence and predictors of hematological abnormalities during treatment of chronic hepatitis C virus (HCV) patients with interferon and ribavirin.

Methods

One thousand and eighty-one chronic HCV patients who were treated with PEGylated interferon α-2a 180 μg (n?=?536) or α-2b 1.5 μg/kg (n?=?545) plus ribavirin for 48 weeks were included. Baseline demographic, laboratory, and histopathological data and, during treatment, hematological data were collected and analyzed using univariate and multivariate analyses to identify independent predictors of hematological side effects.

Results

During therapy, 168 of 1,018 (15.5 %) had moderate anemia (Hb?<10 and ≥8.5 g/dL) and 88 (8.1 %) had severe anemia (Hb?<8.5 g/dL). Two hundred and six patients (19.1 %) had moderate neutropenia (absolute neutrophil count (ANC)?<750 and ≥500/mm³); only 55 (5.1 %) had severe neutropenia (ANC?<500/mm³). Forty-three patients (4 %) had moderate (platelet <50,000 and ≥25,000/mm³) and 5 (1.4 %) had severe thrombocytopenia (platelet <25,000/mm³). Fibrosis stage, week 4 Hb level, and week 2 and 4 reduction level in Hb were independent predictors of moderate and severe anemia (p?<?0.001). Fibrosis stage and ANC at weeks 2 and 4 were predictors of neutropenia (p?<?0.001, 0.001, and 0.004, respectively). Fibrosis stage and platelet count at weeks 2 and 4 were predictors of thrombocytopenia (p?<?0.001, <0.001, and 0.005, respectively). There was no association between interferon type and anemia (p?=?0.57), neutropenia (p?=?0.6), or thrombocytopenia (p?=?0.79).

Conclusions

Fibrosis stage and week 2 and 4 hematological parameter reduction levels were independent predictors of hematological side effects, which are not related to interferon type.     

Slower fibrosis progression in HIV/HCV-coinfected patients with successful HIV suppression using antiretroviral therapy

BACKGROUND/AIMS: HIV/HCV-coinfected patients reportedly have a faster fibrosis progression rate (FPR) than HCV-monoinfected patients. This study examined whether HIV suppression through highly active antiretroviral therapy (HAART) attenuates this accelerated fibrosis progression. METHODS: In two hepatitis C centers, a retrospective analysis identified 656 consecutive treatment-na?ve HCV-infected patients who had undergone a liver biopsy, had a presumed date of HCV infection, and had been tested for HIV, 274 of them HIV-positive (95.2% on HAART) and 382 HIV-negative. The primary outcome measure was the FPR, defined as Ishak fibrosis score [0-6] over estimated duration of HCV infection. RESULTS: Among HIV/HCV-coinfected patients, 51.2% had undetectable HIV RNA (< 400 copies/mL). There was no difference in FPR between HIV/HCV-coinfected and HCV-monoinfected patients (0.136 vs. 0.128 Ishak fibrosis units/year, P=0.29). However, HIV/HCV-coinfected patients with any detectable HIV viral load >400 copies/mL had a faster FPR (0.151) than HCV-monoinfected patients (0.128, P=0.015) and than HIV/HCV-coinfected patients with undetectable plasma HIV RNA (0.122, P=0.013) who in turn had the same FPR as HCV-monoinfected subjects (0.128, P=0.52). An accelerated FPR in HIV viremic patients was seen with CD4+ cells <500/mm(3) (0.162 vs. 0.123, undetectable HIV RNA, P=0.005) but not with CD4+ cells >500/mm(3) (0.118 vs. 0.121, P=0.89). In multivariable linear regression analysis of HIV/HCV-coinfected patients, log(10) HIV RNA level, necroinflammation, and age at HCV infection were independently correlated to FPR, but not alcohol use or CD4+ cell count (r(2)=0.45 for model). CONCLUSIONS: HIV/HCV-coinfected patients with undetectable HIV RNA through HAART have a slower FPR than those with any HIV RNA level and an FPR similar to HCV-monoinfected individuals.     

The relationship between transient elastography and histological collagen proportionate area for assessing fibrosis in chronic viral hepatitis

Background

Collagen proportionate area (CPA) has a better correlation with hepatic venous pressure gradient (HVPG) than with Ishak stage. Liver stiffness measurement (LSM) is proposed as non invasive marker of portal hypertension/disease progression. Our aim was to compare LSM and CPA with Ishak staging in chronic viral hepatitis, and HVPG in HCV hepatitis after transplantation.

Methods

One hundred and sixty-nine consecutive patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections pre/post liver transplantation (LT), had a liver biopsy combined with LSM (transient elastography), CPA (biopsies stained with Sirius Red and evaluated by digital image analysis and expressed as CPA) and HVPG (measured contemporaneously with transjugular biopsies in LT HCV patients).

Results

LSM was dependent on CPA in HBV (r ² = 0.61, p < 0.0001), HCV (r ² = 0.59, p < 0.0001) and LT groups (r ² = 0.64, p < 0.0001). In all three groups, CPA and Ishak were predictors of LSM, but multivariately CPA was better related to LSM (HBV: r ² = 0.61, p < 0.0001; HCV: r ² = 0.59, p < 0.0001; post-LT: r ² = 0.68, p < 0.0001) than Ishak stage. In the LT group, multiple regression analysis including HVPG, LSM, aspartate aminotransferase to platelet ratio index (APRI) and Ishak stage/grade, showed that only CPA was related to HVPG (r ² = 0.41, p = 0.01), both for HVPG ≥6 mmHg (OR 1.34, 95 % CI 1.14–1.58; p < 0.0001) or ≥10 mmHg (OR 1.25, 95 % CI 1.06–1.47; p = 0.007).

Conclusion

CPA was related to LSM in HBV or HCV hepatitis pre/post-LT. CPA was better related to LSM than Ishak stage. In the LT HCV group, CPA was better related to HVPG than Ishak stage/grade, LSM or APRI. CPA may represent a better comparative histological index for LSM, rather than histological stages.     

Racial/Ethnic Differences in Spontaneous HCV Clearance in HIV Infected and Uninfected Women

Background/Aims

Among individuals without human immunodeficiency virus (HIV), African Americans have lower spontaneous clearance of hepatitis C virus (HCV) than Caucasians, and women have higher clearance than men. Few studies report racial/ethnic differences in acute HCV in HIV infected, or Hispanic women. We examined racial/ethnic differences in spontaneous HCV clearance in a population of HCV mono- and co-infected women.

Methods

We conducted a cross sectional study of HCV seropositive women (897 HIV infected and 168 HIV uninfected) followed in the US multicenter, NIH-funded Women’s Interagency HIV Study (WIHS), to determine the association of race/ethnicity with spontaneous HCV clearance, as defined by undetectable HCV RNA at study entry.

Results

Among HIV and HCV seropositive women, 18.7 % were HCV RNA negative, 60.9 % were African American, 19.3 % Hispanic and 17.7 % Caucasian. HIV infected African American women were less likely to spontaneously clear HCV than Hispanic (OR 0.59, 95 % CI 0.38–0.93, p = 0.022) or Caucasian women (OR 0.57, 95 % CI 0.36–0.93, p = 0.023). Among HIV uninfected women, African Americans had less HCV clearance than Hispanics (OR 0.18, 95 % CI 0.07–0.48, p = 0.001) or Caucasians (OR 0.26, 95 % CI 0.09–0.79, p = 0.017). There were no significant differences in HCV clearance between Hispanics and Caucasians, among either HIV infected (OR 0.97, 95 % CI 0.57–1.66, p = 0.91) or uninfected (OR 1.45, 95 % CI 0.56–3.8, p = 0.45) women.

Conclusions

African Americans were less likely to spontaneously clear HCV than Hispanics or Caucasians, regardless of HIV status. No significant differences in spontaneous HCV clearance were observed between Caucasian and Hispanic women. Future studies incorporating IL28B genotype may further explain these observed racial/ethnic differences in spontaneous HCV clearance.     

Extracorporeal Membrane Oxygenation and Retransplantation in Lung Transplantation: An Analysis of the UNOS Registry

Background

Despite limited organ availability, extracorporeal membrane oxygenation (ECMO) and retransplantation are becoming more commonplace.

Methods

Using the United Network for Organ Sharing (UNOS) database, we evaluated survival of patients treated with ECMO before lung transplantation and undergoing retransplantation. A query identified cadaveric recipients from 2001 to 2012 over the age of 6 years.

Results

Of 15,772 lung recipients, 15 583 never received ECMO, whereas 189 did. Mean age was 52.1 ± 14.4 versus 46.8 ± 16.5 years for non-ECMO and ECMO groups, respectively (p < 0.0001). Using Kaplan–Meier method, there were survival differences between ECMO and non-ECMO groups (p < 0.0001) and first-time transplants with and without ECMO to retransplants with and without ECMO (p < 0.0001). The proportional hazards model identified higher risk with ECMO use in idiopathic pulmonary fibrosis (hazard ratio [HR] 1.09; 95 % confidence interval (CI), 1.02–1.17; p = 0.014) and retransplants (HR 1.77; 95 % CI, 1.55–2.03; p < 0.0001).

Conclusions

Survival for retransplantation was similar to ECMO as a primary option with significant mortality associated with ECMO use in patients with idiopathic pulmonary fibrosis and retransplants.     

Comparison of cognitive performance in HIV or HCV mono-infected and HIV–HCV co-infected patients

Purpose

Our aim was to explore the interplay between human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections in the expression of cognitive disorders.

Methods

We performed a multi-centre cross-sectional study, enrolling three groups of asymptomatic outpatients matched for age and education: (1) HIV mono-infected; (2) HCV mono-infected; (3) HIV–HCV co-infected. All subjects were subjected to the Zung depression scale and a comprehensive neuropsychological battery.

Results

A total of 50 patients for each group were enrolled. Patients in the three groups did not significantly differ in the main common demographic and clinical characteristics, except for a lower proportion of past injecting drug use (IDU) in group 1 (4 %) in comparison to groups 2 (38 %, p < 0.001) and 3 (78 %, p < 0.001), a longer duration of HIV infection in group 3 in comparison to group 1 (p < 0.001) and a longer duration of HCV infection in group 3 in comparison to group 2 (p = 0.028). Overall, 39.3 % of patients showed minor cognitive impairment, with a higher proportion in group 3 (54 %) when compared to groups 1 (28 %, p = 0.015) or 2 (36 %, p = 0.108). Patients in group 3 [odds ratio (OR) 3.35, p = 0.038 when compared to group 1] and those with higher depression scores (OR 1.05, p = 0.017) showed an increased risk of cognitive impairment after adjusting for education and past injection drug use. In particular, group 3 showed worse performance in psychomotor speed tasks when compared to group 1 (p = 0.033).

Conclusions

A worse cognitive performance in HIV–HCV co-infected patients was observed, suggesting an additive role of the two viruses in the pathogenesis of cognitive disorders.     

Liver fibrosis on account of chronic hepatitis C is more severe in HIV-positive than HIV-negative patients despite antiretroviral therapy

Summary.  The recent availability of non-invasive tools to measure liver fibrosis has allowed examination of its extent and determination of predictors in all patients with chronic hepatitis C virus (HCV) infection. On the other hand, most information on hepatic fibrosis in HCV/human immunodeficiency virus (HIV)-coinfected patients has been derived from liver biopsies taken before highly active antiretroviral therapy (HAART) was widely available. All consecutive HCV patients with elevated aminotransferases seen during the last 3 years were evaluated and liver fibrosis measured using transient elastography (FibroScan^®) and biochemical indexes. Patients were split according to their HIV serostatus. A total of 656 (69.6%) HCV-monoinfected and 287 (30.4%) HIV/HCV-coinfected patients were assessed. Mean CD4 count of coinfected patients was 493 cells/μL and 88% were under HAART (mean time, 4.2 ± 2.4 years). Advanced liver fibrosis or cirrhosis was recognized in 39% of the coinfected and 18% of the monoinfected patients ( P  < 0.005). A good correlation was found between FibroScan^® and biochemical indexes [AST to platelet ratio index ( r  = 0.405, P  < 0.0001), FIB-4 (r = 0.393, P  < 0.0001) and Forns ( r  = 0.407, P  < 0.0001)], regardless of the HIV status. In the multivariate analysis, age >45 years, body mass index (BMI) >25 kg/m², and HIV infection were independently associated with advanced liver fibrosis or cirrhosis. HIV/HCV-coinfected patients have more advanced liver fibrosis than HCV-monoinfected patients despite the immunologic benefit of HAART.     

Using early viral kinetics to predict antiviral outcome in response-guided pegylated interferon plus ribavirin therapy among patients with hepatitis C virus genotype 1

Background

HCV kinetics during treatment demonstrated strong association with the antiviral outcome of patients treated with pegylated interferon (Peg-IFN) plus ribavirin. However, the relationship between HCV kinetics and pre-treatment factors remains unclear.

Methods

Of 547 patients with HCV genotype 1 treated with Peg-IFN alfa-2b plus ribavirin, 401 completed the response-guided therapy and were assessed for per protocol analysis.

Results

The sustained virologic response (SVR) rate was 53 % for all patients, 60 % for those with genotype TT, and 19 % for those with genotype TG/GG according to IL28B (rs8099917) single nucleotide polymorphisms. The SVR rates increased with HCV decrease at week 4; 4 % (2/56) with <1 log₁₀ decrease, 13 % (7/56) with 1–2 log₁₀ decrease, 51 % (44/87) with 2–3 log₁₀ decrease, 64 % (56/87) with 3–4 log₁₀ decrease, 88 % (72/82) with more than 4 log₁₀ decrease but with detectable HCV RNA and 100 % (33/33) with undetectable HCV RNA (p < 0.001). Similarly, SVR rates increased step-by-step in proportion to HCV decrease in both IL28B TT and TG/GG groups, showing almost the same SVR rates for the same conditions. In multivariate analysis, age (p = 0.005) and the magnitude of HCV decrease at week 4 (p < 0.001) but not IL28B were associated with SVR. Advanced liver fibrosis (p = 0.004) and the magnitude of HCV decrease at week 4 (p < 0.001) but not IL28B were associated with non-response.

Conclusions

The magnitude of the HCV decrease at week 4 seems to be the most reliable marker for predicting antiviral outcome after starting Peg-IFN plus ribavirin therapy.     

Comparison of hepatitis B surface antigen and e antigen in predicting liver histology in hepatitis B e antigen-positive chronic hepatitis B patients

Background/Aim

The purpose of this study was to determine the relationship between hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) levels and liver histology in HBeAg-positive patients with chronic hepatitis B virus (CHB) infection.

Methods

Serum HBsAg and HBeAg levels were analyzed, and liver biopsies were obtained from 203 HBeAg-positive CHB patients (62.6 % males; median age 31.3 years). The upper limit of normal (ULN) for ALT in this study was 30 and 19 U/L for males and females, respectively. Histologic assessment was based on Scheuer classification.

Results

ALT <2 × ULN, fibrosis stage <S2, and necro-inflammation grade <G2 were noted in 70 (34.5 %), 141 (69.5 %), and 105 (51.7 %) patients, respectively. Patients with significant histology (fibrosis stage ≥S2 and/or fibrosis stage of 1 plus inflammation grade ≥2) had significantly lower median HBsAg (13,998.4 and 42,186.5 IU/mL, respectively, p < 0.001) and HBeAg levels (540.5 and 1,206.8 S/CO, respectively, p < 0.001) than patients with insignificant histology. Among patients with ALT <2 × ULN, the area under the ROC curve for serum HBsAg and HBeAg levels was 0.76 and 0.70, respectively. Using a cutoff value of 17,558 IU/mL for HBsAg and 875.6 S/CO for HBeAg in patients with ALT <2×ULN, positive predictive values for insignificant histology were 87 and 86.8 %, respectively, whereas the negative predictive values were 50 and 47.1 %, respectively.

Conclusions

Among HBeAg-positive patients with ALT <2 × ULN, high-serum HBsAg and HBeAg levels can equally accurately predict insignificant histology.     

Incidence of hepatocellular carcinoma in HCV-infected patients with normal alanine aminotransferase levels categorized by Japanese treatment guidelines

Background

This study was conducted to evaluate Japanese treatment guidelines for patients with chronic hepatitis C virus (HCV) infection and normal alanine aminotransferase (N-ALT) levels from the viewpoint of the incidence of hepatocellular carcinoma (HCC).

Methods

Four groups of patients with chronic HCV infection treated with pegylated interferon (Peg-IFN) plus ribavirin, and classified according to the N-ALT guidelines, were examined for HCC incidence: group A (n = 353), ALT ≤30 IU/L and platelet (PLT) ≥15 × 10⁴/mm³; group B (n = 123), ALT ≤30 IU/L and PLT <15 × 10⁴/mm³; group C (n = 233), 30 < ALT ≤ 40 IU/L and PLT ≥15 × 10⁴/mm³; and group D (n = 100), 30 < ALT ≤ 40 IU/L and PLT <15 × 10⁴/mm³. The mean observation period was 36.2 ± 16.5 months

Results

In groups A and C, the HCC incidence was low even in patients with non-response (NR) (cumulative rates at 3 years, 0.0 and 2.9 %, respectively). In groups B and D, 14.5 and 5.3 % of NR patients had developed HCC at 3 years, but none of the patients with sustained virologic response (SVR) or relapse had developed HCC. In group B, no patients with mild fibrosis developed HCC irrespective of the antiviral effect of the treatment. Among patients with PLT <15 × 10⁴/mm³ (group B plus group D), the HCC incidence was significantly lower in patients with SVR and relapse than in NR patients (p < 0.001, p = 0.021, respectively).

Conclusion

These results suggest that N-ALT patients with PLT <15 × 10⁴/mm³ could be candidates for early antiviral therapy.     

Liver Stiffness Measurements in Patients with Different Stages of Nonalcoholic Fatty Liver Disease: Diagnostic Performance and Clinicopathological Correlation

Background

The present study evaluated performance characteristics of liver stiffness measurement (LSM) by FibroScan in patients with different stages of nonalcoholic fatty liver disease (NAFLD).

Patients and Methods

A total of 307 subjects (120 NAFLD, 85 NAFLD related cirrhosis, and 102 healthy controls) were studied.

Results

In NAFLD patients, LSM had significant correlation with fibrosis (r = 0.68, p < 0.001), and increased progressively with increasing fibrosis (p < 0.001). However, the difference between stage 1 and stage 2 fibrosis was not significant (p = 0.07). The LSM in NAFLD without fibrosis and healthy controls was similar (p = 0.37). The areas under receiver-operating characteristics (AUROC) curve of LSM for stages ≥1, ≥2, ≥3, and 4 were 0.82, 0.85, 0.94, and 0.96, respectively. The best LSM (kPa) cut-offs for fibrosis stages ≥1, ≥2, ≥3 and 4 were 6.1, 7.0, 9.0, and 11.8, respectively. The negative predictive value of LSM for excluding advanced fibrosis was 95 %. For advanced fibrosis, the AUROC curve of LSM was 0.94, followed by FIB-4 (0.75), BARD score (0.68), NAFLD fibrosis score (0.66), and aspartate platelet ratio index (0.60). In multivariate analysis, LSM was the only independent predictor of advanced fibrosis (odds ratio 1.47). In patients with NAFLD cirrhosis, LSM correlated significantly with Child-Pugh score (r = 0.40, p < 0.001), serum bilirubin (r = 0.34, p = 0.02), and grades of esophageal varices (r = 0.23, p = 0.04).

Conclusion

LSM is a useful tool for evaluation of patients with NAFLD, and is the best among other non-invasive predictors of liver fibrosis.     

Microscopic esophagitis distinguishes patients with non-erosive reflux disease from those with functional heartburn

Background

Microscopic esophagitis (ME) is common in patients with non-erosive reflux disease (NERD), and dilation of intercellular spaces (DIS) has been regarded as the potential main mechanism of symptom generation. We aimed to compare these histological abnormalities in healthy volunteers (HVs) and patients with erosive esophagitis (EE), NERD, and functional heartburn (FH).

Methods

Consecutive patients with heartburn prospectively underwent upper endoscopy and impedance-pH off-therapy. Twenty EE patients and fifty-seven endoscopy-negative patients (NERD), subclassified as 22 with pH-POS (positive for abnormal acid exposure), 20 with hypersensitive esophagus (HE; normal acid/symptom association probability [SAP]+ or symptom index [SI]+), and 15 with FH (normal acid/SAP-/SI-/ proton pump inhibitor [PPI] test-), were enrolled. Twenty HVs were also included. In each patient/control, multiple specimens (n = 5) were taken from the distal esophagus and histological alterations were evaluated. ME was diagnosed when the global histological score was >0.35.

Results

The prevalence of ME was higher (p < 0.0001) in EE (95 %), pH-POS (77 %), and HE (65 %) NERD patients than in FH patients (13 %) and HVs (15 %). Also, basal cell hyperplasia (p < 0.0023), DIS (p < 0.0001), and papillae elongation (p < 0.0002) showed similar rates of prevalence in the above populations (p < 0.0001). ME, including each histological lesion, had similar low frequencies in FH and HVs (p = 0.9990). Considering the histological abnormalities together, they permitted us to clearly differentiate EE and NERD from FH and HVs (p < 0.0001 and p < 0.0001, respectively).

Conclusions

The lack of ME in the esophageal distal biopsies of FH patients indicates a limited role of these histological abnormalities in symptom generation in them. ME can be considered as an accurate and reliable diagnostic marker for distinguishing FH patients from GERD patients and has the potential to be used to guide the correct therapy.     

Hepatitis C viremia interferes with serum hepatitis B virus surface antigen and DNA levels in hepatitis B uremics

Purpose

Hepatitis B virus (HBV) and HCV might cause reciprocal interference. We aimed to elucidate the influence of HCV and interleukin-28B (IL-28B) genetic variants in the HBV DNA and HBsAg levels in uremic HBV carriers.

Methods

Assessment of HCV and HBV viral loads, HBsAg levels and IL-28B genotype were performed in 229 HBsAg-positive patients from a cohort of 1,681 uremics.

Results

Patients with HCV viremia had significantly lower HBV DNA (2.58 ± 0.80 vs. 3.16 ± 1.48 log IU/mL, p = 0.005) and HBsAg levels (1.33 ± 1.35 vs. 2.23 ± 1.31 log IU/mL, p = 0.002) compared with those without. IL-28B rs8099917 genotype had no impact on HBsAg and HBV DNA levels. In multivariate regression analysis, HCV RNA levels had a more significant negative correlation with HBsAg levels [β ?0.905; 95 % confidence interval (CI) ?1.477, ?0.334; p = 0.002] than with HBV DNA levels (β ?0.586; 95 % CI ?1.206, 0.034; p = 0.06). The serum HBV DNA and HBsAg levels had a positive correlation (r = 0.43, p < 0.001) among the 215 HBeAg-negative patients. However, the correlation was not observed in patients with HCV viremia (r = 0.23, p = 0.29). Linear regression analysis revealed that age (β ?0.286; 95 % CI ?0.043, ?0.014; p < 0.001) and the HBV DNA level (β 0.373; 95 % CI 0.239, 0.549; p < 0.001) correlated independently with the HBsAg level among HBeAg-negative patients without HCV viremia, but not among those with concomitant HCV viremia.

Conclusions

HCV viremia suppressed both HBsAg and HBV DNA levels. The HBsAg levels correlated with the HBV DNA levels only in patients without concomitant HCV viremia.     

Predictive value of FIB-4 and APRI versus METAVIR on sustained virologic response in genotype 1 hepatitis C patients

Purpose

Advanced liver fibrosis is a negative predictor of virologic response in genotype 1 chronic hepatitis C (CHC) patients. Biopsy, however, is invasive, costly, and carries some risk of complications.

Methods

Using data from the prospective, international cohort study PROPHESYS, we assessed two alternative noninvasive measures of fibrosis, the FIB-4 and AST-to-platelet ratio index (APRI), to predict virologic response in CHC patients.

Results

CHC genotype 1, monoinfected, treatment-naive patients prescribed peginterferon alfa-2a (40 KD)/ribavirin in accordance with country-specific legal and regulatory requirements and who had baseline METAVIR, FIB-4, and APRI scores (N = 1,592) were included in this analysis. Patients were stratified according to the baseline METAVIR, FIB-4, or APRI score to assess virologic response [hepatitis C virus (HCV) RNA <50 IU/mL] by week 4 of treatment (rapid virologic response) and 24 weeks after untreated follow-up ]sustained virologic response (SVR)]. Baseline predictors of SVR were explored by multiple logistic regression, and the strength of the association between each fibrosis measure and SVR was evaluated. Both FIB-4 and APRI scores increased with increasing levels of biopsy-assessed fibrosis. The association between FIB-4 and SVR (p < 0.1 × 10^?30) was stronger than that between METAVIR (p = 3.86 × 10^?13) or APRI (p = 5.48 × 10^?6) and SVR. Baseline factors significantly associated with SVR included male gender, lower HCV RNA, lower FIB-4 score, no steatosis, and higher alanine aminotransferase ratio.

Conclusion

The FIB-4 index provides a valuable, noninvasive measure of fibrosis and can be used to predict virologic response in patients treated with peginterferon alfa-2a (40  KD)/ribavirin.     

Correlates of disease-specific knowledge among patients with chronic hepatitis B or hepatitis C infection in India

Background

Patient knowledge about chronic diseases increases health-promoting behaviors and improves clinical outcomes. We assessed this association for patients with chronic viral hepatitis.

Methods

Untreated patients chronically infected with HBV (n = 500) or HCV (n = 500) were enrolled at 19 centers across India. A survey, adapted from the US CDC National Health and Nutrition Examination Survey (NHANES) questionnaire, was administered at a single visit to assess HBV/HCV knowledge, community disease awareness, treatment quality, and healthcare barriers. We developed the India Hepatitis Knowledge Index (IHKI), where a higher IHKI score (range 0–10) indicates increased hepatitis knowledge. Multivariate regression models evaluated demographic and disease factors.

Results

The overall mean IHKI score was 5.6 out of 10, with higher scores among patients with HBV (5.9) than HCV (5.3); p < 0.001. In HBV patients lower IHKI was associated with shorter disease duration, government clinic attendance (p < 0.0001), fewer personal experiences with HBV (p < 0.0001), and residing in northern India. Among HCV patients, lower IHKI was associated with shorter disease duration, community (p < 0.0001) and government clinic attendance (p < 0.0001), and fewer personal experiences with HCV (p < 0.0001). Among HBV patients, IHKI was independently associated with disease severity as assessed by MELD score, albumin, and APRI. This association was strongest for HBV patients with elevated ALT and HBV DNA >2000 IU/ml. Among HCV patients, IHKI results had no significant associations with disease severity.

Conclusions

The association of IHKI with disease underscores the need to understand connections between hepatitis knowledge and progression and may guide efforts to address patient education and awareness of chronic viral hepatitis in India.

     

Influence of Age and HBeAg Status on the Correlation Between HBV DNA and Hepatic Inflammation and Fibrosis in Chronic Hepatitis B Patients

Aims

The purpose of this study was to examine the correlation between serum HBV DNA level and the severity of hepatic inflammation and fibrosis in patients with chronic hepatitis B.

Methods

Liver function, serological markers of HBV and serum HBV DNA quantification were assayed in 215 CHB patients who also underwent liver biopsy. Liver pathology was regarded as the evaluation criteria to evaluate the correlation between serum HBV DNA level and the severity of liver inflammation and fibrosis.

Results

Of the 215 patients, 136 were HBeAg-positive and 79 were HBeAg-negative; 134 patients had mild hepatic inflammation and fibrosis and 81 had significant hepatic inflammation and fibrosis in pathological diagnosis. We found that positive correlation between the severity of hepatic inflammation and fibrosis and serum HBV DNA level was only present in HBeAg-negative patients but not HBeAg-positive patients (P < 0.001). Patients’ age was a key factor influencing the correlation between serum HBV DNA level and the severity of hepatic inflammation and fibrosis. the cutoff values to predict the severity of hepatic inflammation and fibrosis were 33.5 and 36 years, respectively. Using 35 years as the cutoff value, positive correlation between serum HBV DNA level and hepatic inflammation and fibrosis was observed in both HBeAg-positive and HBeAg-negative patients aged ≥35 years (P < 0.05), however no correlation was observed in HBeAg-positive patients aged <35 years.

Conclusions

There was positive correlation between serum HBV DNA level and hepatic inflammation and fibrosis in both HBeAg-positive and HBeAg-negative patients’ aged ≥35 years, but in patients aged <35 years, positive correlation was only observed in HBeAg-negative patients.     

Serum hepatitis B surface antigen (HBsAg) kinetics in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B

Background

We investigated the differences in HBsAg kinetics at different levels of viremia in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB).

Methods

We compared HBsAg levels among HBeAg-negative CHB patients with persistently undetectable HBV DNA (≤20 IU/mL; Group A, n = 100), HBV DNA 20–2,000 IU/mL (Group B, n = 100), and HBV DNA >2,000 IU/mL (Group C, n = 100). HBsAg and HBV DNA levels were measured at three consecutive time points during follow-up (median 21.4 months).

Results

Median HBsAg levels were significantly lower in Group A than in Groups B and C at all time points (p < 0.001). HBV DNA and HBsAg levels were weakly correlated (r = 0.180 and 0.151 for Groups B and C, respectively). Among patients with HBsAg <100 IU/mL, Group A patients had the greatest median serum HBsAg reduction (0.341 log IU/mL/year; Group B, 0.122 log IU/mL/year; Group C, 0.057 log IU/mL/year; p = 0.002). Among Group A patients with HBsAg <100 IU/mL, baseline HBsAg achieved an AUROC of 0.876 in predicting >1 log annual HBsAg reduction; 10–100 IU/mL HBsAg was the optimal level for prediction (sensitivity 90 %; specificity 74.6 %). Serum HBsAg/HBV DNA ratios were significantly higher in Group B than in Groups A and C (p < 0.05).

Conclusions

HBV DNA and HBsAg were weakly correlated. Only patients with undetectable HBV DNA showed decline in HBsAg levels during follow-up. The greatest reduction in HBsAg levels occurred in patients with baseline HBsAg <100 IU/mL.