Impact of Anti-Thymocyte Globulin During Immunosuppression Induction in Patients with Hepatitis C After Liver Transplantation

Background

Induction immunosuppression with anti-thymocyte globulin (ATG) provides potential benefits after liver transplantation (LT). However, its use in patients with LT and hepatitis C (HCV) is controversial.

Aim

To evaluate the 1- and 2-year patient survival and HCV recurrence rate in patients receiving ATG during the induction phase of immunosuppression (IPI) after LT.

Methods

A total of 49 patients undergoing their first LT for HCV were randomized to receive ATG during IPI. Patient survival and HCV recurrence were determined at 1 and 2 years. The frequency of acute cellular rejection (ACR), infections, and neoplasms was also evaluated.

Results

Twenty-six patients were randomized to receive ATG (Arm-1) and 23 to standard induction therapy (Arm-2). Those given ATG had lower HCV recurrence (26.9 vs 73.9 %, p = 0.001). The 1- and 2-year patient survival rates were similar for both arms (p = 0.33). Infections occurred in 46.1 % subjects in Arm-1 and 34.7 % in Arm-2 (p = 0.562). There was a greater proportion of fungal infections in Arm-1 (19.2 vs 0 %, p = 0.032).

Conclusions

ATG during the IPI was associated with lower frequency of recurrence of HCV in patients undergoing LT. This, however, did not affect the 1- and 2-year survival and the frequency of ACR, infections, or neoplasms.     

Hepatitis C viral load predicts tumor recurrence after curative resection of hepatocellular carcinoma regardless of the genotype of hepatitis C virus

Purpose

To clarify the prognostic impact of the hepatitis C virus (HCV) genotype after curative resection for hepatocellular carcinoma (HCC).

Methods

A total of 199 patients who underwent a curative hepatic resection for HCV-related HCC were reviewed. The clinical outcomes were compared between patients infected with HCV genotype 1b (n = 160) and those infected with other genotypes (n = 39).

Results

With a comparable median HCV viral load (6.0 vs. 5.8 log₁₀ IU/mL, p = 0.17), the 3-year recurrence-free survival (RFS) rates (25 vs. 20 %, p = 0.65) and the 5-year overall survival (OS) rates (72 vs. 65 %, p = 0.73) were similar between the two groups. A multivariate analysis confirmed that HCV viral load of +1.0 log₁₀ IU/mL [hazard ratio (HR), 1.48], major vascular invasion (HR, 3.20), recurrent tumor (HR, 1.77), and preoperative des-gamma carboxyprothrombin level >40 mAu/mL (HR, 1.64) were independent predictors of tumor recurrence, while the HCV genotype was not a significant risk factor. When the population was stratified according to the HCV viral load, a significant difference was observed in the RFS rate for both genotype 1b (p = 0.003) and the other genotypes (p = 0.037) at HCV viral load of 5.3 log₁₀ IU/mL.

Conclusions

The HCV genotype does not affect the surgical outcomes of patients with HCC. A lower HCV viral load is advantageous regardless of the HCV genotype.     

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.     

Alcoholism worsens the survival of patients with hepatitis B virus and C virus-related hepatocellular carcinoma

Background/Aims

Chronic hepatitis B and hepatitis C virus (HBV, HCV) infection and alcoholism are common etiologies for hepatocellular carcinoma (HCC). The characteristics and impact of alcoholism and/or HCV/HBV infection on HBV- and HCV-related HCC, respectively, are investigated in this study.

Methods

A total of 1,888 patients were retrospectively investigated and categorized into six groups, HBV only (n = 977), HBV with alcoholism (n = 197), HCV only (n = 544), HCV with alcoholism (n = 67), dual HBV and HCV (n = 82), and dual virus with alcoholism (n = 21), to examine their interactions on the outcome.

Results

Compared to their counterparts, alcoholic patients coinfected with HBV and/or HCV tended to be younger, had higher male-to-female ratios, worse performance status, more severe liver cirrhosis, advanced cancer staging, and tumor burden than patients without alcoholism. In survival analysis, patients with HBV with alcoholism had a significantly decreased survival than the HBV-only group (p = 0.001). A shortened survival was also observed in HCV with alcoholism group compared to the HCV-only group (p = 0.011). Dual virus infection with alcoholism did not significantly worsen the survival compared to the dual virus infection group. In the Cox proportional hazards model, HBV with alcoholism group [risk ratio (RR) 1.299, p = 0.032] and HCV with alcoholism (RR 1.523, p = 0.025) group were independent predictors associated with decreased survival compared to their counterpart of HBV- and HCV-only groups.

Conclusions

Alcoholism in patients with HBV or HCV infection is characterized by early development of HCC with advanced cirrhosis and cancer staging at diagnosis. Alcoholism independently predicts an increased risk of mortality in patients with HBV- and HCV-related HCC.     

Analysis of the complete open reading frame of hepatitis C virus in genotype 2a infection reveals critical sites influencing the response to peginterferon and ribavirin therapy

Purpose

A proportion of patients infected with genotype 2a hepatitis C virus (HCV) cannot achieve a sustained virological response (SVR) to pegylated-interferon plus ribavirin therapy (PEG-IFN/RBV) but the reason remains unclear. The present study aimed to clarify the possible correlation between viral sequence variations and final outcome.

Methods

The pretreatment complete open reading frame (ORF) sequences of genotype 2a HCV were determined by direct sequencing for two independent groups of patients (43 patients as test; group 1 and 35 as validation; group 2), and the correlation with the final outcome was explored.

Results

Patients with SVR (n = 58) and with non-SVR (n = 20) differed significantly in pretreatment HCV RNA level (p = 0.002), fibrosis score (p = 0.047), and cumulative RBV dosage (p = 0.003). By comparison of all amino acid positions in the complete HCV ORFs, threonine at amino acid (aa) 110 in the core region was remarkably frequent in SVR (p = 0.01 for group 1, p = 0.004 for group 2, and p = 5E?05 for combined). A sliding window analysis revealed that the total number of amino acid variations within the NS5A aa 2258–2306 region were significantly high in SVR compared to non-SVR patients (p = 0.01 for group 1, p = 0.006 for group 2, and p = 0.0006 for combined). Multivariate analyses revealed that core aa 110 (p = 0.02), NS5A aa 2258–2306 (p = 0.03), and cumulative RBV dosage (p = 0.02) were identified as independent variables associated with the final outcome.

Conclusions

The outcome of PEG-IFN/RBV therapy is significantly influenced by variation in the core and NS5A regions in genotype 2a HCV infection.     

Prognostic value of ERCC1 in head and neck carcinoma treated with definitive or adjuvant radiotherapy

Purpose

To evaluate the prognostic significance of excision repair cross-complementation group 1 (ERCC1) expression in head and neck carcinoma patients treated with definitive radiotherapy (DR) or adjuvant radiotherapy (AR).

Methods

ERCC1 expression was assessed by immunohistochemical staining. A total of 48 patients were assessed.

Results

High ERCC1 expression was found in 23 patients (48 %). More ERCC1-positive tumours were detected in patients treated with DR than in patients treated with AR (73 vs. 36 %, respectively, p = 0.03). ERCC1 expression had no impact on overall survival neither in the whole cohort of patients (p = 0.16) nor in each particular treatment group (AR p = 0.98; DR p = 0.21).

Conclusions

ERCC1 expression had no predictive value in head and neck carcinoma patients treated with DR or AR. There might be difference in ERCC1 positivity that comes out of whether the assessment is done on biopsy or surgical specimens.     

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.     

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.     

IL28B polymorphisms predict the virological response to standard therapy in patients with chronic hepatitis C virus genotype 4 infection

Background

Genome-wide association studies have recently revealed that several single-nucleotide polymorphisms (SNPs) in the interleukin (IL) 28B genes can predict the sustained virological response (SVR) to pegylated interferon-α2a/b plus ribavirin in hepatitis C virus (HCV)-genotype 1 patients. However, data for patients infected with HCV genotype 4 (HCV-G4) are limited.

Aim

We analyzed the association of IL28B SNPs (hematological, biochemical, virological, and pathological factors) with SVR in the HCV-G4 monoinfected cohort of patients.

Patients and methods

One hundred twenty-nine treatment-naïve HCV-G4 patients undergoing treatment were recruited from three tertiary care centers in Saudi Arabia. Five IL28B SNPs (rs12979860, rs12980275, rs8105790, rs8099917, and rs72486680) were identified by polymerase chain reaction and DNA sequencing. SVR was statistically correlated with various clinical, histopathological, virological, and genetic parameters.

Results

SVR was significantly associated with the CC and AA alleles of rs12979860 (p = 0.008) and rs12980275 (p = 0.004), respectively. Moreover, albumin levels (p = 0.002) and platelet count (p = 0.039) showed significant differences in the SVR and No SVR groups. On multivariate analysis, the CC allele of rs12979860 (OR, 2.89; 95 % CI 1.6–6.2, p = 0.006) and albumin levels (OR, 1.2; 95 % CI 1.1–1.4, p = 0.001) independently predicted SVR.

Conclusions

IL28B polymorphism (CC allele of rs12979860) predicts the sustained response to antiviral therapy in HCV-G4.     

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.     

Hepatic Preservation Injury: Severity of Hepatitis C Recurrence and Survival After Liver Transplantation

Background

Preservation injury in the HCV liver transplant population has been reported to correlate with poorer survival outcomes compared to preservation injury in the non-HCV liver transplant population. However, determinants of progression to cirrhosis in HCV infection remain poorly defined in this population.

Aim

This study aimed to determine if the presence and severity of preservation injury impact the acceleration of HCV recurrence and survival after liver transplant.

Methods

We retrospectively reviewed liver transplant HCV patients over a 10-year period. Biopsies from postoperative day 7 were assessed for preservation injury and 4- and 12-month biopsies were assessed for fibrosis. Patients with Ishak fibrosis >0.8 Units/year were considered rapid fibrosers.

Results

Our study group consisted of 255 patients. The mean age was 49.3 years old, 180 (70.6 %) were male, and 221 (86.7 %) were Caucasian. The incidence of preservation injury on the 7-day biopsy was 69.0 %. A strong correlation between postoperative peak AST within the first week and preservation injury was found. The overall prevalence of rapid fibrosers at 4 months, 1 and 2 years was 47.4, 75.2, and 58.9 %, respectively. The prevalence of rapid fibrosers at 4 months, 1 and 2 years between patients with or without preservation injury was not statistically significant (p = 0.39, p = 0.46, and p = 0.53, respectively). No differences were seen between patients with and without PI in terms of patient and graft survival.

Conclusion

In this study, the presence and severity of preservation injury were not associated with development of rapid HCV recurrence or worsening in survival.     

Dual treatment of acute HCV infection in HIV co-infection: influence of HCV genotype upon treatment outcome

Purpose

With DAAs still only being licensed for chronic HCV infection, the ongoing epidemic of acute hepatitis C (AHC) infection among MSM highlights the need to identify factors allowing for optimal HCV treatment outcome.

Methods

303 HIV-infected patients from 4 European countries with diagnosed acute HCV infection were treated early with pegylated interferon (pegIFN) and ribavirin (RBV) (n = 273) or pegylated interferon alone (n = 30).

Results

All patients were male, median age was 39 years. Main routes of transmission were MSM (95 %) and IVDU (3 %). 69 % of patients were infected with HCV GT 1, 4.3 % with GT 2, 10.6 % with GT 3, 16.1 % with GT 4. Overall SVR rate was 69.3 % (210/303). RVR (p ≤ 0.001), 48-w treatment duration (p ≤ 0.001) and GT 2/3 (p = 0.024) were significantly associated with SVR. SVR rates were significantly higher in HCV GT 2/3 receiving pegIFN and RBV (33/35) when compared with pegIFN mono-therapy (6/10) (94 % vs. 60 % respectively; p = 0.016). In multivariate analysis, pegIFN/RBV combination therapy (p = 0.017) and rapid virological response (RVR) (p = 0.022) were significantly associated with SVR in HCV GT 2/3. In HCV GT 1/4, RVR (p ≤ 0.001) and 48-w treatment duration (p ≤ 0.001) were significantly associated with SVR.

Conclusions

Treatment of AHC GT 2 and 3 infections with pegIFN/RBV is associated with higher SVR rates suggesting different cure rates depending on HCV genotype similar to the genotype effects seen previously in chronic HCV under pegIFN/RBV. With pegIFN/RBV still being the gold standard of AHC treatment and in light of cost issues around DAAs and very limited licensed interferon-free DAA treatment options for chronic HCV GT 3 infection AHC GT 3 patients might benefit most from early interferon-containing treatment.

     

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.     

The safety and efficacy of peginterferon plus ribavirin in hepatitis C patients concomitant with malignancy other than hepatocellular carcinoma: a multicenter study

Purpose

Cancer patients were generally excluded from the therapeutic guidelines of antiviral therapy. We aimed to evaluate the efficacy and safety of antiviral therapy in patients with hepatitis C virus (HCV) infection concomitant with malignancy other than hepatocellular carcinoma (HCC).

Methods

Twenty-five HCV patients with curative malignancy other than HCC (group A) and 75 sex- and age-matched controls (group B) were recruited into a prospective and case–control analysis. All patients received peginterferon-alpha-2a (PegIFN-alpha-2a) and weight-based ribavirin according to the current treatment recommendations. The primary outcome measurement was sustained virological response (SVR). The safety issue between groups was also compared.

Results

There were 22 (88.0 %) patients of group A and 59 (78.7 %) patients of group B who achieved an SVR (p = 0.39). The SVR rate was comparable between groups both in genotype-1 (HCV-1) (81.8 vs. 72.7 %, p = 0.70) and in genotype-2 (HCV-2) (92.9 vs. 83.3 %, p = 0.66) patients. Multivariate logistic regression analysis demonstrated that the achievement of a RVR (viral clearance during first 4 weeks of treatment) was the strongest predictor of an SVR (odds ratio/95 % confidence intervals [OR/CI]: 6.357/1.50 ? 26.99, p = 0.01), followed by lower baseline viral loads (OR/CI: 0.403/0.174 ? 0.936, p = 0.034) and higher dose of ribavirin exposure (OR/CI: 1.287/1.092 ? 1.517, p = 0.003), whilst previous occurrence of cancer was not associated with SVR. Treatment adherence (76.0 vs. 72.0 %, p = 0.70) and the incidences of grade 3 or more adverse events (28.0 vs. 20.0 %, p = 0.40) were comparable between two groups.

Conclusions

Chronic hepatitis C patients with non-HCC malignancies receiving peginterferon/ribavirin combination therapy carried favorable efficacy and safety outcomes.     

Long-term outcome of neoadjuvant systemic therapy for locally advanced breast cancer in routine clinical practice

Purpose

The aim of this study is to evaluate the long-term outcome of patients with locally advanced breast cancer treated with neoadjuvant systemic chemotherapy (NST) in routine clinical practice.

Methods

Four hundred and nine patients were identified between January 1999 and December 2011. All patients received NST followed by surgery, adjuvant treatments and radiotherapy, as appropriate.

Results

At Kaplan–Meier analysis, patients with surgical stage III disease were more likely to develop distant metastasis and die from breast cancer (p < 0.001). Luminal A and luminal B/HER2-negative patients had better prognosis; moreover, patients with hormone receptor (HR)-positive tumors had a significantly longer DRFS (p < 0.0049) and OS (p < 0.0001) compared with patients with HR-negative tumors as well as patients who underwent breast-conserving surgery (DRFS and OS: p < 0.001). In multivariate analysis, HR negativity (p < 0.001 for both DRFS and OS), mastectomy (DRFS: p = 0.009; OS: p = 0.05) and stage III disease (DRFS: p < 0.001; OS: p = 0.003) were associated with shorter DRFS and OS.

Conclusions

HR negativity, mastectomy and pathological stage III disease are the variables independently associated with a worse outcome in our cohort of patients. These data are of high interest since they derive from a very heterogeneous group of patients, treated with different neoadjuvant/adjuvant regimens outside of clinical trials and with a long follow-up period.     

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.     

Is transarterial chemoembolization beneficial for patients with diffuse infiltrative hepatocellular carcinoma?

Purpose

Diffuse infiltrative hepatocellular carcinoma (D-HCC) is an incurable disease with short survival time. Transarterial chemoembolization (TACE) was often used to alleviate patient’s symptoms and reduce tumor burden. However, it remains unknown if the TACE benefits the survival of D-HCC patients.

Methods

A hospital-based retrospective study was conducted at a large referral hospital in Taiwan for a 9-year period (2000–2008).

Results

Of the 150 D-HCC patients, 106 patients were related to hepatitis B virus (HBV), 17 to hepatitis C virus (HCV), 3 to both HBV and HCV, and 24 not to HBV or HCV. Multivariate Cox regression analysis showed treatment strategy, serum alpha-fetoprotein level, model for end-stage liver disease (MELD) score, serum gamma glutamyl transferase, and serum lactic acid dehydrogenase were associated with survival time. Compared to supportive treatment, the adjusted hazard ratios of transarterial chemoembolization (TACE) and chemotherapy including oral or systemic chemotherapy were 0.383 (p < 0.001) and 0.711 (p = 0.289), respectively.

Conclusion

TACE is a preferred therapy for D-HCC patients.     

Factors influencing liver fibrosis and necroinflammation in HIV/HCV coinfection and HCV monoinfection

Objectives

To define differences in liver histology between HIV/HCV coinfection and HCV monoinfection, and to investigate possible causative factors.

Methods

Liver biopsies (LBs) from 440 consecutive HIV/HCV-coinfected patients (Group HIV/HCV) and 374 consecutive HCV-monoinfected patients (Group HCV) were evaluated for necroinflammation and fibrosis (Ishak) by a pathologist unaware of the clinical and laboratory data. All patients were HBsAg-negative, with no history of alcohol abuse and naïve to anti-HCV treatment. At LB, 78.4 % of patients in Group HIV/HCV were on an antiretroviral regimen.

Results

HIV/HCV-coinfected patients compared to the HCV-monoinfected patients were younger (p < 0.0001), more frequently males (p < 0.0001), and had HCV genotype 3 (p < 0.0001); they showed a good immunological condition (CD4+ cell count: 518 ± 166 cells/mm³). Patients in Group HIV/HCV more frequently showed a fibrosis score ≥4 (27.5 vs. 20.6 %, p < 0.05) and a necroinflammation score ≥9 (25.9 vs. 13.4 %; p < 0.0001). The prevalence of patients with fibrosis score ≥4 was significantly higher in older age classes in both Group HIV/HCV (p < 0.005) and Group HCV (p < 0.05). A necroinflammation score ≥9 was significantly higher in older age classes only in Group HIV/HCV (p < 0.05). A multivariate analysis for Group HIV/HCV revealed that the patient age and nadir of CD4+ cell count were independently associated to higher degrees of fibrosis, the patient age and antiretroviral treatment were associated to higher degrees of necroinflammation, and HCV genotype 3 was associated to higher degrees of steatosis.

Conclusion

The data suggest a need for early anti-HCV treatment in both HCV-monoinfected and HIV/HCV-coinfected patients.     

Laparoscopic liver resection for treating recurrent hepatocellular carcinoma

Background

It is still unknown whether laparoscopic liver resection is suitable for recurrent hepatocellular carcinoma (HCC) after previous curative hepatic resection.

Method

The perioperative outcomes of 40 patients treated with second surgery for recurrent HCC by partial hepatectomy were studied retrospectively. The second surgery was performed under laparotomy in 20 patients (laparotomy group) and under laparoscopy in 20 patients (laparoscopy group).

Results

Intraoperative blood loss (p < 0.0001) and the incidence of postoperative complications (p = 0.0004) were lower in the laparoscopy group than in the laparotomy group. The incidence rates of surgical site infection and intractable ascites were significantly higher in the laparotomy group than in the laparoscopy group (p = 0.0202, p = 0.0436, respectively). The proportion of patients classified as Clavien grade IIIa was higher in the laparotomy group than in the laparoscopy group (p = 0.0033). The duration of the postoperative hospital stay was significantly shorter in the laparoscopy group than in the laparotomy group (p < 0.0001).

Conclusions

Postoperative morbidity has been decreased by the introduction of laparoscopic liver resection in patients with recurrent HCC after curative hepatic resection. As a result, the duration of the postoperative stay is shorter.