Dimitrios Tzourmakliotis

Outcome of hepatitis B e antigen–negative chronic hepatitis B on long‐term nucleos(t)ide analog therapy starting with lamivudine

We determined the clinical outcome of hepatitis e antigen (HBeAg)‐negative chronic hepatitis B patients treated with long‐term nucleos(t)ide analog therapy starting with lamivudine. We evaluated 201 such patients treated for 3.8 ± 1.4 years and 2 historical similar cohorts: 1 treated with interferon‐alfa (n = 209) and 1 untreated (n = 195). Virological or biochemical remission rate at 48 months under lamivudine was 34% or 36%, respectively, whereas adefovir was administered in 79 patients with virological–biochemical breakthroughs or no response. Of the lamivudine‐treated patients, 4 died, 1 underwent a transplantation, and another 8 developed major events, all having advanced fibrosis at baseline and all but 1 having experienced breakthroughs or no response. At 5 years, survival was 96%, and major event–free survival was 93%. The major event–free survival was significantly better in patients with than in those without virological remission under lamivudine. At the end of follow‐up, both survival and major event–free survival were independently associated with type of and response to treatment, being significantly better in patients under long‐term antiviral therapy or interferon sustained responders than in interferon non‐sustained responders or untreated cases (5‐year survival: 96% or 98% vs. 88% or 90%, respectively). In conclusion, in HBeAg‐negative chronic hepatitis B, long‐term nucleos(t)ide analog therapy starting with lamivudine significantly improves survival and reduces the risk of major complications, compared with interferon non‐sustained responders or untreated patients. In such patients with advanced fibrosis, close follow‐up for lamivudine resistance and prompt onset of additional antiviral therapy is required or the ab initio use of agent(s) with low resistance rates should be considered. (HEPATOLOGY 2005;42:121–129.)

Is there a meaningful serum hepatitis B virus DNA cutoff level for therapeutic decisions in hepatitis B e antigen–negative chronic hepatitis B virus infection?

The diagnosis of hepatitis B e antigen (HBeAg)‐negative chronic hepatitis B indicating therapeutic intervention currently requires serum hepatitis B virus (HBV) DNA ≥2,000 IU/mL. We evaluated the severity of liver histology and the presence of histological indication for treatment in patients with HBeAg‐negative chronic HBV infection focusing on those with low viremia and/or normal alanine aminotransferase (ALT). In total, 399 patients with increased ALT and detectable serum HBV DNA (chronic hepatitis B patients) and 35 cases with persistently normal ALT and HBV DNA >2,000 IU/mL (inactive carriers) were included. Histological indication for treatment (grading score ≥7 and/or stage ≥2 in Ishaks classification) was found in 91% (185/203), 82% (75/91), 75% (47/63), and 62% (26/42) of chronic hepatitis B patients with HBV DNA ≥200,000, 20,000‐199,999, 2,000‐19,999, and <2,000 IU/mL, respectively (P < 0.001). Histological indication for treatment was more frequent in chronic hepatitis B patients with persistently elevated ALT (86% or 275/321), but it was also found in 74% (58/78) of those with transiently normal ALT (P = 0.025). All inactive carriers had HBV DNA <20,000 IU/mL. Histological indication for treatment was present in 17% (6/35) of inactive carriers always due to moderate (stage 2) fibrosis without active necroinflammation. Conclusion: HBeAg‐negative chronic HBV patients with persistently or transiently increased ALT and HBV DNA ≥20,000 IU/mL almost always require therapeutic intervention, but histological indications for treatment are also present in the majority of such cases with HBV DNA <20,000 and even <2,000 IU/mL. In contrast, minimal histological lesions are observed in the majority of HBeAg‐negative patients with persistently normal ALT and HBV DNA >2,000 IU/mL, who may not require immediate liver biopsy and treatment but only close follow‐up. (HEPATOLOGY 2008.)

Does clinical response correlate with mucosal healing in patients with Crohn's disease of the small bowel? A prospective, case-series study using wireless capsule endoscopy.

Background: There are no studies assessing mucosal healing of the small bowel in patients with Crohns disease (CD). Our aim was to assess the correlation between clinical response and mucosal healing of the small bowel using wireless capsule endoscopy (WCE). Methods: This was a prospective, multicenter, case‐series study. Forty patients with known or suspected CD were included, recruited in 4 tertiary referral centers of Athens. They all had an acute flare‐up of their disease (CD Activity Index [CDAI] >150), involvement of the small bowel, and the nonstricturing, nonpenetrating type of the disease. All patients underwent WCE prior to the initiation of any treatment. Treatment varied according to the treating physician. For the evaluation of mucosal healing, 3 endoscopic variables were collected: number of apthous ulcers, number of large ulcers, and period of time that any endoscopic lesion was visible (erythema, edema, ulcers). When patients achieved clinical response (after at least a month of treatment) they underwent a second WCE, with evaluation of the same parameters. Results: The number of large ulcers was the only endoscopic variable that showed a significant improvement. The numbers of large ulcers before and after treatment were 8.3 ± 1.4 and 5 ± 0.8, respectively (mean ± SEM) (mean difference 3.3 ± 1.2, 95% confidence interval [CI] 0.8–5.9, P = 0.01). The other 2 variables did not improve significantly. Conclusions: Since only 1 out of 3 endoscopic variables improved significantly with treatment, we can conclude that clinical response does not seem to correlate with mucosal healing in patients with CD of the small bowel.

Clinical Course of Lamivudine Monotherapy in Patients with Decompensated Cirrhosis due to HBeAg negative chronic HBV infection

OBJECTIVES:We have evaluated the efficacy of long-term lamivudine monotherapy in patients with decompensated HBeAg-negative/HBV-DNA positive cirrhosis.METHODS:We analyzed the clinical course and outcome of lamivudine treatment in 30 consecutive cirrhotics and compared with 30 HBV untreated historical HBeAg-negative controls matched for age and gender.RESULTS:Significant clinical improvement, defined as a reduction of at least two points in Child-Pugh score was observed in 23 of the 30 treated patients (76.6%) versus none of the 30 patients in the control group (p < 0.0001) after a mean follow-up of 20.6 ± 12.1(±SD) months. There were 10 deaths in the treated group versus 24 in the control group (p= 0.07). Liver-related deaths occurred in five of the eight patients soon after the development of biochemical breakthrough. Patients with clinical improvement had better survival than patients with no improvement (p= 0.04) or those who developed biochemical breakthrough due to YMDD mutants (p= 0.001).CONCLUSIONS:Lamivudine significantly improves liver function in HBeAg-negative decompensated cirrhosis. However, the development of the biochemical breakthrough due to YMDD mutants is associated with fatal outcome.

Antiviral therapy reduces portal pressure in patients with cirrhosis due to HBeAg-negative chronic hepatitis B and significant portal hypertension

BACKGROUND/AIMS Lamivudine improves liver histology in patients with chronic hepatitis B (CHB), but its effects on portal pressure remain unknown. We evaluated the effect of lamivudine monotherapy on hepatic venous pressure gradient (HVPG) in CHB-related cirrhosis with significant portal hypertension. METHODS We studied 19 patients with cirrhosis due to HBeAg-negative CHB and HVPG >or=10 mm Hg treated with oral lamivudine (100mg daily). Liver biochemistry, Child-Pugh and MELD score were determined every 3 months, alpha-fetoprotein and HBV DNA every 6 months and HVPG at baseline and at 12 months after lamivudine initiation. Diuretics, beta-blockers, antibiotics and/or endoscopic therapy were used for routine indications. RESULTS At 12 months, a significant reduction was observed in ALT (p=0.001), HBV DNA (p=0.002), Child-Pugh (p=0.012) and MELD score (p=0.006). Four patients developed virological breakthrough during treatment. At 12 months, HVPG decreased in all but one patient [baseline: 14.4+/-3.9 and 12 months: 12.4+/-3.3 mm Hg (p=0.007)]. HVPG decreased >20% or below the 12 mm Hg threshold in 10 of 13 patients with baseline HVPG >or=12 mm Hg. HVPG increased in a patient with hepatic flare after virological breakthrough. CONCLUSION In conclusion, in patients with cirrhosis due to HBeAg-negative CHB, lamivudine monotherapy reduces HVPG, especially when virological suppression and biochemical remission is achieved.

Primary prophylaxis of variceal bleeding in cirrhotics unable to take beta-blockers: a randomized trial of ligation.

Aim : To compare endoscopic banding ligation vs. no treatment in cirrhotics with intolerance or contraindications to β‐blockers for prevention of first bleeding in portal hypertension.

Long-term therapy with adefovir dipivoxil in hepatitis B e antigen-negative patients developing resistance to lamivudine

Background  The efficacy of long‐term adefovir dipivoxil monotherapy or combination of adefovir and lamivudine in hepatitis B e antigen (HBe‐Ag)‐negative lamivudine‐resistant chronic hepatitis B (CHB) patients is still under investigation.

An assessment of serum leptin levels in patients with chronic viral hepatitis: a prospective study

BackgroundThe role of leptin in the course of liver disease due to chronic viral hepatitis (CVH) remains controversial. Our aims were to investigate the relationship between serum leptin concentrations and the severity of liver disease in a cohort of subjects with HBeAg negative chronic hepatitis B (CHB) and C (CHC) and to analyze the effect of body composition, the leptin system and insulin resistance together with viral factors on virologic response to antiviral treatment.MethodsWe studied 50 (36 men) consecutive patients suffering from biopsy-proven CVH due to HBV (n = 25) or HCV (n = 25) infection. Thirty-two (17 men) healthy volunteers served as controls. Levels of serum leptin and insulin were determined by immunoassays at baseline and at the end of the treatment.ResultsA significant association between serum leptin levels and the stage of hepatic fibrosis was noted; patients with cirrhosis presented higher serum leptin levels compared to those with lower fibrosis stage [CHB patients (17436 pg/ml vs 6028.5 pg/ml, p = 0.03), CHC patients (18014 pg/ml vs 4385 pg/ml, p = 0.05]. An inverse correlation between lower leptin levels and response to lamivudine monotherapy was noted in patients with CHB; those with a virologic response presented lower serum leptin levels (5334 vs 13111.5 pg/ml; p-value = 0.003) than non-responders. In genotype 1 CHC patients, insulin resistance played a significant role in the response to antiviral therapy.ConclusionOur data clearly suggest that cirrhosis due to CHB or CHC is associated with higher leptin levels. Increased serum leptin levels represent a negative prognostic factor for response to lamivudine monotherapy in patients with CHB. In CHC patients insulin resistance strongly influences the response to antiviral treatment in patients infected with genotype 1.

Ultrasound‐guided liver biopsy in real life: Comparison of same‐day prebiopsy versus real‐time ultrasound approach

Background and Aim:  Currently, an increasing number of liver biopsies are performed by radiologists under real‐time ultrasound control. A routine ultrasound assessment of a puncture site before performing percutaneous biopsy is reported to increase diagnostic yield and decrease complication rates. It is not clear if real‐time ultrasound is superior to marking the puncture site before biopsy as regards reducing biopsy size and avoiding fragmentation and complications. The aim of this study was to compare ultrasound assessment of the puncture site before performing percutaneous liver biopsy with real‐time ultrasound liver biopsy for suspected diffuse liver disease.

Serum HCV RNA levels and HCV genotype do not affect insulin resistance in nondiabetic patients with chronic hepatitis C: a multicentre study.

Background  Chronic hepatitis C (CHC) induces insulin resistance (IR) and subsequently diabetes.