S. Gaia

Reliability of transient elastography for the detection of fibrosis in Non-Alcoholic Fatty Liver Disease and chronic viral hepatitis

BACKGROUND & AIMS Transient elastography (TE) is validated in chronic hepatitis C (CHC) to evaluate hepatic fibrosis; however, limited data are available in chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD). This prospective study is aimed to assess the accuracy and the efficacy of TE for the detection of fibrosis in patients with chronic liver disease of different etiology and to evaluate the effect of steatosis on the liver stiffness measurement (LSM). METHODS TE was performed in 219 consecutive patients with chronic liver disease (35% CHC, 32% CHB, and 33% NAFLD) within 6 months of the liver biopsy. RESULTS LSM was related to the fibrosis stage in each group (CHC: p = 0.596, p < 0.001; CHB: p = 0.418, p < 0.001; NAFLD: p = 0.573, p < 0.001), but the correlation was less strong in CHB and NAFLD than in CHC patients. In CHB patients with histological cirrhosis (F4), the median stiffness value was almost two times lower than in patients with severe fibrosis (F3). In NAFLD patients with advanced fibrosis (F3) and severe steatosis (> 33%), the LSM values were lower than expected and were similar to those of patients with initial fibrosis (F1) and fat < 33%. TE underestimated the stage of fibrosis in 75% of patients with F3 and steatosis > 33%. At multiple logistic regression analysis, in CHC and CHB patients, LSM was the only predictive variable of severe fibrosis/cirrhosis (OR = 1.42, p = 0.003 and OR = 1.354, p = 0.003, respectively), while in NAFLD subjects BMI and AST (OR = 1.433, p = 0.002 and OR = 1.053, p = 0.020, respectively) but not LSM were independently related with advanced fibrosis and cirrhosis. CONCLUSIONS This study confirms that TE can be considered a valid support to detect fibrosis in chronic liver disease related to HCV but it should be interpreted cautiously in CHB and NAFLD patients, where host or disease-related factors may modify its accuracy.

Viral load at the time of liver transplantation and risk of hepatitis B virus recurrence

Hepatitis B virus (HBV) recurrence after liver transplantation is significantly reduced by prophylaxis with hepatitis B immune globulins (HBIG) or antiviral drugs in nonreplicating patients and by the combination of both drugs in replicating patients. However, the load of HBV DNA, which defines replicating status in patients undergoing liver transplantation, remains unclear. This study analyzes the correlation between the viral load, tested with a single amplified assay, at the time of liver transplantation, and the risk of hepatitis B recurrence in 177 HBV carriers who underwent transplantation in a single center from 1990 to 2002. Overall, HBV relapsed after surgery in 15 patients (8.5%) with a 5‐ and 8‐year actuarial rate of recurrence of 8% and 21%, respectively. After liver transplantation hepatitis B recurred in 9% of 98 selected subjects treated only with immune globulins and in 8% of 79 viremic patients who received immune globulins and lamivudine (P = NS). A linear correlation was observed between recurrence and viral load at the time of surgery. In transplant patients with HBV DNA higher than 100,000 copies/mL, 200–99,999 copies/mL, and DNA undetectable by amplified assay, hepatitis B recurred in 50%, 7.5%, and 0% of patients, respectively. Overall, a viral load higher than 100,000 copies/mL at the time of liver transplantation was significantly associated with hepatitis B recurrence (P = .0003). In conclusion, spontaneous or antiviral‐induced HBV DNA viral load at the time of surgery classifies the risk of HBV recurrence after liver transplantation and indicates the best prophylaxis strategy. (Liver Transpl 2005;11:402–409.)

Occult hepatitis B virus infection in HBsAg negative patients undergoing liver transplantation: Clinical significance

Occult Hepatitis B virus (o‐HBV) infection has been reported in HB surface antigen (HBsAg)‐negative liver donors whose risk of transmitting HBV justifies a specific prophylaxis in liver recipients. The clinical significance of o‐HBV infection in HBsAg‐negative recipients and their need for prophylaxis is unknown. Liver samples collected during surgery from 23 HBsAg‐negative patients (9 liver donors and 14 recipients) and 20 HBsAg‐positive recipients (controls) were studied by polymerase chain reaction with an independent set of primers mapping the core and surface HBV genes. Intrahepatic HBV DNA was detected as core and surface genes in all the HBsAg‐positive recipients, in none of the HBsAg‐negative donors and in 9/14 (64%) of the HBsAg‐negative recipients (2 HCV negative, 7 HCV positive). The intrahepatic amount of HBV was significantly lower in HBsAg‐negative than in HBsAg‐positive livers (median values 1.36 Log10/μg DNA vs. 3.66 Logs, p<0.0001, core gene, and 1.13 vs. 6.21 Logs p<0.0001, surface gene). No HBV DNA was detected in plasma from o‐HBV recipients; one of them tested positive in lymphocytes. No correlation was found between o‐HBV and serologic markers of previous HBV exposure, response to vaccination, acute rejection, hepatitis D and G virus‐infections. None of o‐HBV carriers experienced a de novo hepatitis B after transplantation (median follow‐up: 477 days). Occult HBV is frequent in HBsAg‐negative liver recipients. It is not associated with increased episodes of acute rejection, coinfection with hepatotropic viruses, different responses to HBV vaccination, or the development of de‐novo hepatitis B. In o‐HBV infection a particular virus‐host interaction can explain the low intrahepatic HBV content and the lack of extrahepatic HBV replication, thus justifying the low risk of hepatitis B reactivation, in absence of specific prophylaxis, once the recipient liver is removed. (Liver Transpl 2004;10:356–362.)

Lamivudine-resistant chronic hepatitis B: An observational study on adefovir in monotherapy or in combination with lamivudine ☆

BACKGROUND/AIMS In lamivudine-resistant patients with chronic hepatitis B (CHB), we compared efficacy, predictive response factors and changes in viral mutants in two antiviral approaches with adefovir. METHODS A prospective cohort study on therapy with adefovir alone (29 patients) or combined with ongoing lamivudine (23 patients) was performed. RESULTS A virological response was achieved in 55% of patients treated with adefovir and in 83% of those treated with the combination (p>0.05). This response was directly related to the basal viral load (p<0.0001) and obtained in 10 patients with basal HBV-DNA<17,200 IU/ml using both strategies. In patients with a higher basal viral load, the virological response was more frequent when treated with the combination (p<0.05). Mutation at locus rt181 predicted HBV-DNA persistence during therapy. A virological rebound was observed in 18% of non-responders while on adefovir monotherapy. CONCLUSIONS To achieve a complete virological response and reduce the risk of adefovir-resistant mutants in lamivudine-resistant patients, rescue therapy is preferable at early evidence of genotypic resistance. However, in subjects with a significant viral load, combination therapy is more effective. The presence of the rt181 mutation is associated with incomplete response.

Application of the model for end-stage liver disease score for transjugular intrahepatic portosystemic shunt in cirrhotic patients with refractory ascites and renal impairment.

Background and aims Transjugular intrahepatic portosystemic shunt (TIPS) can manage severe complications of portal hypertension. The Mayo Clinic group proposed a so-called model for end-stage liver disease (MELD) to predict survival in cirrhotic patients. High creatinine levels determine a decrease in calculated survival chances with MELD but functional renal disease can be reversed by TIPS. The aim of this study was to evaluate the efficacy of MELD in predicting survival after TIPS, particularly in patients with refractory ascites associated with functional renal failure. Methods This retrospective analysis examines 68 cirrhotic patients who underwent elective TIPS: 48 patients had refractory ascites and 20 patients had recurrent variceal bleeding. Multivariate analysis was used to establish predictive parameters of survival after TIPS. Kaplan–Meier and log-rank tests were used to compare survival rates observed in our patients with those evaluated with the MELD score. Results The age of patients was the only variable shown to have an independent value in predicting survival after TIPS. In patients undergoing shunting for refractory ascites, the survival rates at 6, 12 and 24 months after the procedure were significantly higher than expected with the MELD score. Conclusions The MELD scale may underestimate the efficacy of TIPS in end-stage cirrhotic patients with refractory ascites and functional kidney dysfunction. Further studies are needed to confirm this finding and ultimately to assess a correction factor to better predict survival after TIPS in patients with functional renal impairment.

Highly sensitive alpha‐fetoprotein, Lens culinaris agglutinin‐reactive fraction of alpha‐fetoprotein and des‐gamma‐carboxyprothrombin for hepatocellular carcinoma detection

Hepatocellular carcinoma (HCC) develops with high incidence in patients with chronic liver disease (CLD), and particularly in those with cirrhosis. Currently, diagnosis and surveillance are mainly based on imaging methods. The aim of this study was to evaluate the diagnostic accuracy of highly sensitive measurement of α‐fetoprotein (AFP), Lens culinaris agglutinin‐reactive fraction of AFP (AFP‐L3) and des‐γ‐carboxyprothrombin (DCP) alone and in combination, for HCC detection. In addition, a recently proposed statistical model, including these three biomarkers plus sex and age, the GALAD model, was applied.

Temporary Endoscopic Metallic Stent for Idiopathic Esophageal Achalasia

Idiopathic achalasia is a motor disorder of the esophagus of unknown etiology caused by loss of motor neurons determining an altered motility. It may determine severe symptoms such as progressive dysphagia, regurgitations, and pulmonary aspirations. Many therapeutic options may be offered to patients with achalasia, from surgery to endoscopic treatments such as pneumatic dilation, botulinum injection, peroral endoscopic myotomy, or endoscopic stenting. Recently, temporary placement of a stent was proposed by Cheng as therapy for achalasia disorders, whereas no Western authors have dealt with it up to date. The present study reports our preliminary experience in 7 patients with achalasia treated with a temporary stent. Partially covered self-expanding metallic stents (Micro-Tech, Nanjin, China) 80 mm long and 30 mm wide were placed under fluoroscopic control and removed after 6 days. Clinical follow-up was scheduled to check endoscopic success, symptoms release, and complications. The placement and the removal of the stents were obtained in all patients without complications. Mean clinical follow-up was 19 months. Five out of 7 patients referred total symptoms release and 2 experienced significant improvement of dysphagia. The procedure was not time consuming and was safe; no mild or severe complications were registered. In conclusion, our results may suggest a possible safe and effective endoscopic alternative treatment in patients with achalasia; however, further larger studies are necessary to confirm these promising, but very preliminary, data.

Radiofrequency ablation: technical and clinical long-term outcomes for single hepatocellular carcinoma up to 30 mm.

Background and aims Western guidelines consider radiofrequency ablation (RF) as the standard treatment for ‘very early’ and ‘early’ hepatocellular carcinoma (HCC) in nonsurgical cirrhotic patients. RF has also been proposed as the first-line therapy for ‘surgical’ candidates with a single nodule of 20 mm or less. The aim of this monocentric cohort study was to evaluate the technical and clinical outcomes of RF in the treatment of cirrhotic patients with a single HCC of 30 mm or less. Patients and methods We included all 209 consecutive patients treated between January 2001 and June 2011. The primary endpoints were the overall survival (OS) rate and safety; the secondary endpoints were primary technique effectiveness, local tumor progression, and the disease-free survival rate. Results The 5-year OS rate of the entire sample was 44.3% (95% confidence interval: 36.7–55.8); Child–Pugh class B was the worst negative prognostic factor (hazard ratio: 2.06; P=0.008). A subgroup of 70 Child–Pugh class A patients suitable for surgical resection according to current Western operability criteria showed a 5-year OS rate of 60.6%. Treatment-related mortality and morbidity rates were 0 and 3.4%, respectively. Primary technique effectiveness rate was 95.2% after one to three RF sessions. The 5-year cumulative incidence of local tumor progression was 21.5 and 32.5% for nodules ⩽20 and 21–30 mm, respectively. The 5-year disease-free survival rate (comprehensive of any kind of tumor progression or death) was 17.8% (95% confidence interval: 11.1–25.8). Conclusion RF is an effective and very safe therapy for HCC up to 30 mm; in ‘surgical’ cirrhotic patients, the OS rate was similar to those reported in surgical series, although the local recurrence rate was higher.

Non‐invasive score system for fibrosis in chronic hepatitis: proposal for a model based on biochemical, FibroScan and ultrasound data

We elaborate a non‐invasive score system for liver fibrosis (NISF), exploring its diagnostic performance and comparing its accuracy to FibroScan in patients with chronic viral hepatitis (CH) and non‐alcoholic fatty liver disease (NAFLD).

Inactive hepatitis B virus carriers: a favourable clinical condition.

It has recently been reported that inactive chronic hepatitis B virus (HBV) carriers do not seem to develop clinically significant liver disease or liver complications over long periods of follow-up [1]. The inactive chronic HBV carrier status is characterized by the presence of hepatitis B surface antigen (HBsAg) in the serum for at least 6 months, persistently normal serum transaminase levels, hepatitis e antigen negativity, hepatitis e antibody positivity in the most part, undetectable HBV-DNA levels in the serum by non-amplified methods, and the absence of significant hepatitis (necro-inflammatory score lower than 4, optional criteria) [2,3]. The course and the outcome of this condition is generally considered to be benign, but some studies [4–6] reported equivocal data on survival, with slightly increased morbidity and mortality rates for liver disease.