Themistoklis Vasiliadis

Virological suppression does not prevent the development of hepatocellular carcinoma in HBeAg-negative chronic hepatitis B patients with cirrhosis receiving oral antiviral(s) starting with lamivudine monotherapy: results of the nationwide HEPNET. Greece cohort study

Objective To evaluate the risk and predictors of hepatocellular carcinoma (HCC) in HBeAg-negative chronic hepatitis B patients of the large HEPNET.Greece cohort study who received long-term oral antivirals starting with lamivudine monotherapy. Design Retrospective analysis of HCC incidence in HBeAg-negative chronic hepatitis B patients from a retrospective–prospective cohort who were treated with nucleos(t)ide analogue(s) starting with lamivudine monotherapy for ≥12 months. Setting A nationwide network of liver centres. Patients 818 patients were included: 517 with chronic hepatitis B only; 160 with compensated cirrhosis; 56 with decompensated cirrhosis; 85 with unclassified disease severity. Interventions All patients were treated with nucleos(t)ide analogue(s) starting with lamivudine monotherapy. Main outcome measures Development of HCC. Results During a median follow-up of 4.7 years, HCC developed in 49 (6.0%) patients. The 5-year cumulative incidence of HCC was higher in patients with cirrhosis than in those with chronic hepatitis B only (11.5% vs 3.2%, respectively; p<0.001). HCC developed in 0.7%, 6.7% and 11.7% of patients <50, 50–60 and >60 years old, respectively (p<0.001). Virological on-therapy remission did not significantly affect the incidence of HCC in all patients or those with cirrhosis, but it showed a trend for lower HCC incidence in patients with chronic hepatitis B only (p=0.076). In multivariate analysis, age, gender and cirrhosis were independently associated with HCC risk regardless of virological remission. Conclusions Long-term therapy with nucleos(t)ide analogue(s) starting with lamivudine monotherapy does not eliminate HCC risk in HBeAg-negative chronic hepatitis B. The risk of HCC is particularly high in patients with cirrhosis, who should remain under HCC surveillance even during effective therapy. Older age and male gender remain independent risk factors for HCC, while virological on-therapy remission does not seem to significantly reduce the overall incidence of HCC.

Hepatitis B prophylaxis post liver transplantation with newer nucleos(t)ide analogues after hepatitis B immunoglobulin discontinuation

Newer nucleos(t)ide analogues (NUCs) have better resistance profiles making hepatitis B immunoglobulin (HBIG)‐sparing protocol an attractive prophylactic approach against hepatitis B virus (HBV) recurrence after liver transplantation (LT). We evaluated the risk of HBV recurrence after withdrawal of HBIG in patients who had been under HBIG plus NUCs after LT. Stable patients without HBV recurrence after LT while receiving combination of HBIG plus NUCs for at least 12 months were eligible for HBIG discontinuation. The patients were at low risk for HBV recurrence (only 4.5% had detectable HBV DNA at the time of LT, and 32% had HBV/hepatitis D virus co‐infection). All patients were followed up with HBV serum markers, HBV‐DNA, and evaluation of renal function, including glomerular filtration rate. Forty‐seven recipients discontinued HBIG and were maintained on newer NUCs. Median follow‐up post‐HBIG withdrawal was 24 months (range: 6–40 months). Twenty‐eight (60%) patients continued on lamivudine in combination with adefovir dipivoxil (n = 23, 82%) or tenofovir (n = 5, 18%); 10 (21%) and 9 (19%) of the 47 patients continued on tenofovir and entecavir monoprophylaxis, respectively. Although 3 (6.3%) patients developed detectable hepatitis B surface antigen, all of them had undetectable HBV DNA and no clinical manifestations of HBV recurrence. Renal function was similar between the different groups of patients. In conclusion, maintenance therapy with newer NUCs after discontinuation of HBIG prophylaxis was effective, but further studies in larger cohorts with longer follow‐up are needed.

The use of statins alone, or in combination with pioglitazone and other drugs, for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and related cardiovascular risk. An Expert Panel Statement

Non-alcoholic fatty liver disease (NAFLD), the most common liver disease, is characterized by accumulation of fat (>5% of the liver tissue), in the absence of alcohol abuse or other chronic liver diseases. It is closely related to the epidemic of obesity, metabolic syndrome or type 2 diabetes mellitus (T2DM). NAFLD can cause liver inflammation and progress to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis or hepatocellular cancer (HCC). Nevertheless, cardiovascular disease (CVD) is the most common cause of death in NAFLD/NASH patients. Current guidelines suggest the use of pioglitazone both in patients with T2DM and in those without. The use of statins, though considered safe by the guidelines, have very limited use; only 10% in high CVD risk patients are on statins by tertiary centers in the US. There are data from several animal studies, 5 post hoc analyses of prospective long-term survival studies, and 5 rather small biopsy proven NASH studies, one at baseline and on at the end of the study. All these studies provide data for biochemical and histological improvement of NAFLD/NASH with statins and in the clinical studies large reductions in CVD events in comparison with those also on statins and normal liver. Ezetimibe was also reported to improve NAFLD. Drugs currently in clinical trials seem to have potential for slowing down the evolution of NAFLD and for reducing liver- and CVD-related morbidity and mortality, but it will take time before they are ready to be used in everyday clinical practice. The suggestion of this Expert Panel is that, pending forthcoming randomized clinical trials, physicians should consider using a PPARgamma agonist, such as pioglitazone, or, statin use in those with NAFLD/NASH at high CVD or HCC risk, alone and/or preferably in combination with each other or with ezetimibe, for the primary or secondary prevention of CVD, and the avoidance of cirrhosis, liver transplantation or HCC, bearing in mind that CVD is the main cause of death in NAFLD/NASH patients.

Eradication Therapy in Helicobacter pylori-Positive Patients with Halitosis: Long-Term Outcome

Objective: The aim of this study was to investigate the incidence and long-term outcome of halitosis before and after eradication therapy in patients with functional dyspepsia and Helicobacter pylori infection. Subjects and Methods: Halitosis and dyspepsia-related symptoms were investigated by way of a questionnaire. Only patients with functional dyspepsia, H. pylori infection and no histological evidence of atrophy were included in the study. A total of 18 patients fulfilled these criteria and completed the study. Four to six weeks after the end of eradication treatment, endoscopy or [13C] breath test was performed to check for H. pylori in the gastric mucosa. Halitosis and dyspeptic symptoms were re-evaluated during and at the end of follow-up. Results:H. pylori infection was eradicated in all patients, in the 14/18 patients (77.8%) with triple drug therapy, and the 4/18 patients (22.2%) with quadruple drug therapy. During the follow-up period (mean 55.8 ± 21.3 months (range 6–108 months)) resolution of halitosis was observed in 16/18 patients (88.9%), while 2 patients (11.1%) (p < 0.001) continued to present with halitosis. Also, eradication therapy resulted in statistically significant relief of all dyspeptic symptoms, except bloating. Conclusion: Eradication of H. pylori in patients with functional dyspepsia and halitosis results in sustained resolution of halitosis during long-term follow-up in the majority of cases. This finding supports the existence of a link between H. pylori infection and halitosis and suggests that H. pylori eradication might be considered in patients with halitosis.

Diagnostic yield and clinical impact of capsule endoscopy in obscure gastrointestinal bleeding during routine clinical practice: a single-center experience.

Objective: This study assessed the diagnostic yield of capsule endoscopy (CE) and its impact on patients with obscure gastrointestinal bleeding (OGIB). Subjects and Methods: Between May 2007 and May 2009, 63 patients with OGIB (overt bleeding: 25, and occult blood loss with chronic ferropenic anemia: 38) and normal upper and lower endoscopy were studied by CE. Demographic characteristics, prior diagnostic tests, CE findings, therapeutic interventions, medical treatment and clinical outcomes following CE were evaluated. Results: The overall diagnostic yield was 44.44% of patients and included findings of angiectasia in 11 (17.46%) patients, nonsteroidal anti-inflammatory drugs enteropathy in 6 (9.52%) patients, celiac disease in 3 (4.76%) patients, tumors in 2 (3.17%) patients, and a variety of other diagnoses ranging from varices to ulcers (due to congenital afibrinogenemia and amyloidosis). The diagnostic yield was notably higher in overt bleeders (15/25, 60%) compared to occult bleeders (13/38, 34.21%; p = 0.044), and in patients with overt bleeding who had CE within the first 10 days (14/16, 87.5%) after the bleeding episode in comparison to overt bleeders who underwent CE >10 days after the bleeding episode (2/16, 11.1%; p < 0.0001). During follow-up (11.8 ± 7 months), CE findings led to specific therapy that resolved the underlying disease or improved the clinical condition in 45 of 63 patients, thus having a positive clinical impact of 71.43%. Conclusion: CE has a high diagnostic yield and a positive influence on clinical management in a significant proportion of patients with OGIB. These data further support the role of CE in routine clinical practice.

Endoclipping-assisted resection of large colorectal polyps.

Background The use of endoclipping may minimize the risk of bleeding after endoscopic polypectomy of large pedunculated polyps. The aim of this study was to assess the safety and efficacy of endoclipping of the stalk before resection of large pedunculated colorectal polyps, drawing particular attention to the cases in which the use of this method could be very useful. Patients and Methods This retrospective study included 17 patients [10 men, 7 women; median age: 62 y (range 38 to 79)] with 18 large pedunculated colorectal polyps, who underwent endoclipping-assisted endoscopic polypectomy between March 2003 and May 2006. The outcome of the technique and the technique-related complications were evaluated. Results Application of the clips was possible in all patients. In 4 patients (23.5%), the endoclipping was performed via the more flexible gastroscope. En bloc resection of colon polyps was achieved in all patients. No immediate or late bleeding or perforation occurred. One patient (5.9%) developed postcoagulation syndrome and was successfully treated conservatively. Histologic examination showed in situ carcinoma in 6 polyps (33.3%). Follow-up colonoscopy demonstrated no recurrence of polyps or cancer development. Conclusions Endoclipping, followed by snare transection, may be safer than conventional polypectomy in large pedunculated colorectal polyps. Special attention is needed not to cut very close to clips to avoid thermal injury of colonic wall.

Telbivudine is associated with improvement of renal function in patients transplanted for HBV liver disease

Recent studies showed that telbivudine in patients with hepatitis B virus (HBV) infection improved their glomerular filtration rate (GFR), but data regarding its impact on renal function in liver transplant (LT) recipients are very limited. We evaluated 17 consecutive recipients who received at baseline nucleos(t)ide analogue(s) (NAs) other than telbivudine for 12 months, and then they were switched to telbivudine prophylaxis for another 12 months. In each patient, laboratory data including evaluation of GFR (using MDRD and CKD‐EPI) were prospectively recorded. The changes in GFR (ΔGFR) between baseline and after 12 months (1st period) and between telbivudine initiation and 24 months (2nd period) were evaluated. All patients remained serum HBsAg and HBV‐DNA negative. GFR‐MDRD at baseline, 12 months and 24 months were 72 ± 18, 67.8 ± 16 and 70.3 ± 12mL/min, respectively, (P = 0.025 for comparison between 12 months and 24 months). ΔGFR at the 1st period was significantly lower, compared with ΔGFR at the 2nd period [mean ΔGFR‐MDRD: −4.2 (range: −24–9) vs 2.5 (range: −7–22) mL/min, P = 0.013; mean ΔGFR‐CKD‐EPI: −4.2 (range: −19–10) vs 4.0 (range: −7–23) mL/min, P = 0.004], although the serum levels of calcineurin inhibitors were similar between the two periods. A second group of recipients (n = 17) who remained under the same nontelbivudine NA(s) for 24 months had a decline in the mean eGFR during the total follow‐up period. In conclusion, we showed that telbivudine administration in LT recipients for HBV cirrhosis was effective and it was associated with significant improvement in renal function, but this remains to be confirmed in larger well‐designed studies.

Renal function improvement in liver transplant recipients after early everolimus conversion: A clinical practice cohort study in Spain

A national, multicenter, retrospective study was conducted to assess the results obtained for liver transplant recipients with conversion to everolimus in daily practice. The study included 477 recipients (481 transplantations). Indications for conversion to everolimus were renal dysfunction (32.6% of cases), hepatocellular carcinoma (HCC; 30.2%; prophylactic treatment for 68.9%), and de novo malignancy (29.7%). The median time from transplantation to conversion to everolimus was 68.7 months for de novo malignancy, 23.8 months for renal dysfunction, and 7.1 months for HCC and other indications. During the first year of treatment, mean everolimus trough levels were 5.4 (standard deviation [SD], 2.7) ng/mL and doses remained stable (1.5 mg/day) from the first month after conversion. An everolimus monotherapy regimen was followed by 28.5% of patients at 12 months. Patients with renal dysfunction showed a glomerular filtration rate (4-variable Modification of Diet in Renal Disease) increase of 10.9 mL (baseline mean, 45.8 [SD, 25.3] versus 57.6 [SD, 27.6] mL/minute/1.73 m2) at 3 months after everolimus initiation (P < 0.001), and 6.8 mL at 12 months. Improvement in renal function was higher in patients with early conversion (<1 year). Adverse events were the primary reason for discontinuation in 11.2% of cases. The probability of survival at 3 years after conversion to everolimus was 83.0%, 71.1%, and 59.5% for the renal dysfunction, de novo malignancy, and HCC groups, respectively. Everolimus is a viable option for the treatment of renal dysfunction, and earlier conversion is associated with better recovery of renal function. Prospective studies are needed to confirm advantages in patients with malignancy. Liver Transpl 21:1056-1065, 2015.

Nucleos(t)ide analog(s) prophylaxis after hepatitis B immunoglobulin withdrawal against hepatitis B and D recurrence after liver transplantation.

Nucleos(t)ide analogs (NAs) have made a hepatitis B immunoglobulin (HBIG)‐sparing protocol an attractive approach against hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, this approach is considered controversial in patients transplanted for HBV and hepatitis D (HDV) co‐infection.

Common ABCB1 polymorphisms in Greek patients with chronic hepatitis C infection: A comparison with hyperlipidemic patients and the general population

BACKGROUND Hepatitis C virus infectivity and replication efficiency appears to be dependent on the lipid content and organization of the plasma membrane of the host cell, as well as of the intracellular membranous web. As there is increasing awareness of a role played by the efflux pump ABCB1 (p-glycoprotein, P-gp) in lipid homeostasis, its function could be a determinant of chronic HCV infection. The aim of the present study was to examine and compare the distribution of common ABCB1 genotypes in patients with chronic HCV infection (n=168), hyperlipidemic patients (n=168) and a control group (n=173), all from Greece. METHODS Participants were genotyped for the ABCB12677G>T/A and 3435C>T polymorphisms with previously reported PCR-RFLP methods. Genotype and allele frequency distributions were compared between the three groups with the χ(2) test of independence. RESULTS The ABCB1 2677GG (ancestral) genotypes were significantly over-represented in patients with chronic hepatitis C compared to controls (39.3% vs. 26.6%, p=0.015 according to the dominant model). A similar result was obtained when hyperlipidemic patients were compared to controls (45.2% vs. 26.6%, p<0.001 according to the dominant model). Comparison of ABCB1 3435C>T genotype and allele distributions provided similar but not as significant differences. Genotype and allele distributions for both ABCB12677G>T/A and 3435C>T were very similar between HCV patients and hyperlipidemic patients. CONCLUSION Our findings imply an influence of ABCB1 polymorphisms on HCV infectivity, possibly through an effect on lipid homeostasis.