Hepatology International

Whether the efficacies of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) in treating liver-related outcomes of decompensated chronic hepatitis B (CHB) patients are comparable remained inconclusive. An 8-year cohort study of 736 decompensated CHB patients was conducted, and 65 TDF-treated patients were sex, age and model for end-stage liver disease (MELD) scores-1:4 matched with 260 ETV-treated patients through propensity score-matching method. Of 736 patients, 574 (78%) were male, with a mean age of 54.3 years, 438 (59.5%) had cirrhosis, 147 (20%) were positive for HBeAg, and 84 (11.6%) and 652 (88.4%) were treated with TDF and ETV, respectively. The 652 ETV-treated patients were older, had higher baseline MELD score and rates of encephalopathy, but lower ALT levels than the 84 TDF-treated patients. No significant differences were observed in the cumulative incidences of liver-related mortality or liver transplantation (1-month, 18.45 vs. 14.01%, p = 0.368; 8-year, 39.74 vs. 34.24%, p = 0.298), and hepatocellular carcinoma development (5-year, 7.21 vs.13.17%, p = 0.994; 8-year, 11.60 vs.13.17%, p = 0.857) between the matched 260 ETV- and 65 TDF-treated patients, regardless of time points. Baseline MELD score (subdistribution hazard ratio (sHR): 1.063; 95% confidence interval (CI) of sHR: 1.016–1.112) and hepatic encephalopathy (sHR: 5.127; 95% CI sHR: 3.032–8.669) were independently associated with liver-related mortality or liver transplantation in the matched patients. ETV and TDF had comparable efficacy in the short- and long-term liver-related outcomes of decompensated CHB patients, and baseline liver reserve was associated with the outcomes.

In this study, we developed an ex vivo functional assay to assess liver metabolic capacity adapted from the lidocaïne test in rats. Animals used were subjected to different models of liver injury: hypothermic ischemia (H/I, n = 8), ischemia-reperfusion (I/R, n = 8) and CCl4 induced liver cirrhosis (n = 11), and compared with sham operated rats (n = 5). Livers were then extracted and a fragment of whole tissue was incubated with lidocaïne for 15, 30, 60, 120, 240, 360, and 720 min at which both lidocaïne and its major metabolite monoethylglycinexylidide (MEGX) were measured by high performance liquid chromatography (HPLC). A histological study and biochemical assays (transaminase levels) were also performed to further evaluate and confirm our data. Pharmacokinetic profile of lidocaïne metabolism in sham-operated animals revealed that the maximum concentration of MEGX is achieved at 120 min. Both lidocaïne metabolism and MEGX formation levels were significantly altered in all three models of hepatic injury. The extent of hepatic damage was confirmed by increased levels of transaminase levels and alteration of hepatocyte’s structure with areas of necrosis. Our method provides reliable and reproducible results using only a small portion of liver which allows for a fast and easy assessment of liver metabolic capacity. Moreover, our method presents an alternative to the in vivo technique and seems more feasible in a clinical setting.

Early diagnosis of sepsis in alcoholic hepatitis is important for selecting the appropriate therapy. The role of procalcitonin (PCT) to diagnose sepsis in patients with alcoholic hepatitis and systemic inflammatory response syndrome (SIRS) is not yet clear. All patients admitted with alcoholic hepatitis and SIRS underwent measurement of serum PCT and C reactive protein (CRP) levels within 24 h of admission. Patients were classified into two groups: group 1, alcoholic hepatitis with SIRS alone; group 2, alcoholic hepatitis with SIRS and sepsis. The ability of PCT to predict sepsis was evaluated using receiver-operating characteristic (ROC) analyses to compare the two groups. The study included 11 patients in group 1 and 29 in group 2. All were male (median age 42 years; range, 24–65 years). Age, dose and duration of alcohol intake, biochemical parameters and median MELD score were not significantly different between the two groups. PCT and CRP were significantly higher among group 2 than group 1 patients (p < 0.05). ROC analysis showed an AUC of 0.81 (95 % CI 0.66–0.96) and 0.83 (95 % CI 0.68–0.93) for PCT and CRP, respectively, in distinguishing sepsis from SIRS without sepsis. A cutoff level of 0.57 mcg/l for PCT (sensitivity 79 %, specificity 82 %) for diagnosing sepsis in patients with alcoholic hepatitis and SIRS was comparable to a serum CRP cutoff level of 2.3 mg/dl (sensitivity 82.0 %, specificity 75 %). Serum PCT can be a useful marker for diagnosing sepsis in patients with alcoholic hepatitis and SIRS and compares favorably with serum CRP levels.

Long-term treatment with tenofovir disoproxil fumarate (TDF) has demonstrated suppression of viral replication outside of China. This study aims to assess efficacy, resistance and safety of TDF for up to 240 weeks in Chinese patients with chronic hepatitis B virus (HBV) infection. Patients (HBeAg-positive or HBeAg-negative) who were randomised to receive TDF 300 mg or adefovir dipivoxil (ADV) 10 mg once daily in the 48-week double-blind phase (N = 498) were eligible to enter the open-label TDF phase (TDF–TDF and ADV–TDF groups) for additional 192 weeks. Overall, 457/512 (89.3%) randomised patients completed 240 weeks of treatment. Virological suppression was achieved in 84.5% and 87.9% in HBeAg-positive patients and 89.6% and 89.5% in HBeAg-negative patients in TDF–TDF and ADV–TDF groups, respectively, at week 240. The majority of patients from both groups had normalized alanine transaminase levels. More patients had HBeAg loss (41.7% vs. 36.4%) and HBeAg seroconversion (32.0% vs. 28.3%) in TDF–TDF than in ADV–TDF group, respectively. Only one HBeAg-positive patient in TDF–TDF group had HBsAg loss at week 240. No evidence of resistance to TDF was observed. The incidence of adverse events was similar in both groups (TDF–TDF, 56.4% vs. ADV–TDF, 51.6%). One patient had serum creatinine elevation ≥ 0.5 mg/dL above baseline, and three patients had confirmed grade 3/4 phosphorus abnormalities (< 2 mg/dL). In Chinese patients with chronic HBV, long-term treatment with TDF showed sustained viral suppression without development of resistance up to 240 weeks. No new safety concerns were found with TDF in this patient population. Clinical Trial Registration ClinicalTrial.gov Identifier NCT01300234; GSK Clinical Study Register 114648.

Transient elastography has good diagnostic accuracy for predicting fibrosis and cirrhosis related to hepatitis B virus. However, the enrolled subjects in some studies have also included chronic hepatitis B patients with chronic hepatitis C coinfection or other etiologies of liver diseases. This might under- or overestimate the role of transient elastography in chronic hepatitis B patients. A systematic review was conducted on records in PubMed, EMBASE and the Cochrane Library electronic databases until 31 December 2013. We systematically assessed the effectiveness and accuracy of transient elastography for predicting the fibrosis and cirrhosis of the single hepatitis B virus. The questionnaire for quality assessment of diagnostic accuracy studies was used. In this meta-analysis, out of 257 articles evaluated for eligibility, 165 satisfied the predetermined inclusion criteria for meta-analysis. Eventually, our final data set for the meta-analysis contained 19 studies. The areas under the summary receiver-operating characteristic curve for transient elastography of significant fibrosis and cirrhosis were 0.8225 and 0.9108, respectively. The pooled diagnostic odds ratios for transient elastography of significant fibrosis and cirrhosis were 11.19 (95 % CI 6.63–18.89) and 26.87 (95 % CI 17.88–40.38), respectively. In Europe, the areas of significant fibrosis and cirrhosis were 0.803 and 0.905; those in Asia were 0.871 and 0.914, respectively. Based on this meta-analysis we claim that liver stiffness measurement using transient elastography has good diagnostic accuracy for predicting single hepatitis B virus-related significant fibrosis and cirrhosis, especially in Asian populations.

Four single nucleotide polymorphisms (SNPs) exist in the promoter region of the osteopontin (OPN) gene, namely, the SNPs at nucleotide (nt) -155, -616, and -1748 showing linkage disequilibrium to each other, and an independent SNP at nt -443. The significance of these SNPs in the risk of hepatocellular carcinoma (HCC) development was examined in patients with hepatitis C virus (HCV). The SNPs at nt -155 and nt -443 were analyzed in 120 patients with HCC. The promoter activity was measured in HepG2 cells by the dual-luciferase reporter assay. The electrophoretic mobility shift assay was performed using nuclear extracts from the cells. Peripheral platelet counts at the time of HCC detection were greater in women with homozygous deletion at nt -155 and C/C or C/T at nt -443 than in those showing other allelic combinations, while no such difference was observed in men. The promoter activity was greater in oligonucleotides with deletions at nt -155 and C at nt -443 than in those with other haplotypes. The mobility shift assay showed double and single complexes with oligonucleotides around nt -155 and nt -443, respectively. Binding activities were greater in deletion than in G in the case of the retarded complex in the former assay and in T than in C in the latter assay. The other complex in the former assay included SRY, showing an equivalent binding activity to oligonucleotides with both alleles. OPN promoter SNPs may play a role in the sexual difference in the risk of HCC development through the regulation of OPN expression in patients with HCV.

Hepatitis C virus (HCV) has been postulated to be an etiological agent for lymphoid malignancies. Whereas a high prevalence of HCV infection in non-Hodgkin’s lymphoma (NHL) patients has been shown to exist in many geographical areas of high HCV prevalence, studies from other parts have not established any form of association. In India, there is a scarcity of data to show either a positive or a negative association between NHL and HCV infection. Therefore, we determined the prevalence of HCV infection in patients with NHL. A total of 228 subjects were included, out of which, the number of newly diagnosed consecutive patients with lymphoproliferative disorders (NHL and CLL) were 57 [mean age, 48.7 years (range: 18–80)] and the control group consisted of 171 subjects [mean age, 48.6 years (range: 18–80)]. We used third generation enzyme immunoassay to detect HCV antibodies. HCV RNA was detected by nested RT-PCR. Among the 57 patients of NHL, 44 (77.2%) had high-grade disease (diffuse large B cell), 6 (10.5%) intermediate-grade (follicular lymphoma), and 7 (12.3%) low-grade (small lymphocytic); 26 patients had B symptoms at diagnosis. None of the patient tested positive for antibody to hepatitis C virus (anti-HCV) while 1 patient (1.75%) tested positive for HCV RNA. Among the age- and sex- matched controls, 2 (1.17%) subjects tested positive for anti-HCV; both were also positive for HCV RNA. HCV infection is unlikely to be associated with lymphoproliferative disorders in northern India and does not play a major role in the pathogenesis of lymphoproliferative disorders.