Linked color imaging versus narrow-band imaging for colorectal polyp detection: a prospective randomized tandem colonoscopy study.

BACKGROUND AND AIMS: Linked color imaging (LCI) is a newly available image-enhanced endoscopy (IEE) system that emphasizes the red mucosal color. No study has yet compared LCI with other available IEE systems. Our aim was to investigate polyp detection rates using LCI compared with narrow-band imaging (NBI). METHODS: This is a prospective randomized tandem colonoscopy study. Eligible patients who underwent colonoscopy for symptoms or screening/surveillance were randomized in a 1:1 ratio to receive tandem colonoscopy with both colonoscope withdrawals using LCI or NBI. The primary outcome was the polyp detection rate. RESULTS: Two hundred seventy-two patients were randomized (mean age, 62 years; 48.2% male; colonoscopy for symptoms, 72.8%) with 136 in each arm. During the first colonoscopy, the polyp detection rate (71.3% vs 55.9%; P = .008), serrated lesion detection rate (34.6% vs 22.1%; P = .02), and mean number of polyps detected (2.04 vs 1.35; P = .02) were significantly higher in the NBI group than in the LCI group. There was also a trend of higher adenoma detection rate in the NBI group compared with the LCI group (51.5% vs 39.7%, respectively; P = .05). Multivariable analysis confirmed that use of NBI (adjusted odds ratio, 1.99; 95% confidence interval, 1.09-3.68) and withdrawal time >8 minutes (adjusted odds ratio, 5.11; 95% confidence interval, 2.79-9.67) were associated with polyp detection. Overall, 20.5% of polyps and 18.1% of adenomas were missed by the first colonoscopy, but there was no significant difference in the miss rates between the 2 groups. CONCLUSION: NBI was significantly better than LCI for colorectal polyp detection. However, both LCI and NBI missed 20.5% of polyps. (Clinical trial registration number: NCT03336359.).

Territory-wide population-based study of chronic hepatitis C infection and implications for hepatitis elimination in Hong Kong.

BACKGROUND: To study the epidemiology of chronic hepatitis C virus infection in Hong Kong and to estimate the service gap for achieving the WHO hepatitis elimination targets of attaining a diagnosis rate of 90%, treatment rate of 80% and 65% reduction in mortality rate by 2030. METHODS: From January 2005 to March 2017, patients who were tested positive for anti-HCV were retrospectively retrieved from all public hospitals in Hong Kong. The epidemiological data of 15 participating hospitals were analysed. RESULTS: A total of 11 309 anti-HCV+ patients were identified and the estimated diagnosis rate was 50.9%. Our HCV-infected patients were ageing (median age 59). The all-cause mortality rate increased from 26.2 to 54.8 per 1000 person-years over the last decade. Our estimated treatment rate was 12.4%. Among the treated patients, 93.6% had received pegylated interferon/ribavirin (Peg-IFN/RBV) but only 10.8% had received interferon-free direct-acting antivirals (DAAs). In a cohort of 1533 patients, 39% already had advanced liver fibrosis or cirrhosis. The sustained virological response rate for Peg-IFN/RBV and DAAs were 74.8% and 97.2% respectively. However, more than 70% of patients were not subjected to interferon treatment for various reasons. Patients who achieved SVR were associated with a significantly lower risk of HCC (4.7% vs 9.6%, P = 0.005) and death (1.7% vs 23.8%, P < 0.001). CONCLUSION: Our diagnosis rate, treatment rate and mortality rate reduction were still low, particularly the Peg-IFN outcomes, making it difficult to meet the WHO hepatitis elimination targets. A more generalized use of DAAs is urgently needed to improve the situation.

Prevention of post-sphincterotomy bleeding by proton pump inhibitor: A randomized controlled trial.

OBJECTIVE: Post-endoscopic sphincterotomy (EST) bleeding is one of the most frequent complications of endoscopic retrograde cholangiopancreatography (ERCP). Although the use of proton pump inhibitors (PPIs) reduces the risk of peptic ulcer bleeding, their role in preventing EST bleeding has not been evaluated. This study aimed to assess the use of pre-emptive PPIs in patients undergoing EST. METHODS: This was an investigator-initiated, open-label, randomized study. Consecutive patients scheduled to undergo ERCP and EST were enrolled after excluding those who had previous EST or used acid-suppression agents. Eligible patients were randomized to receive either PPI or standard care. The PPI group received intravenous esomeprazole 4 h before the EST and then every 12 h for 1 day, followed by high-dose oral esomeprazole for 10 days. All patients were followed up for 30 days. The primary outcome was the proportion of patients with combined immediate and delayed overt post-EST bleeding. RESULTS: Altogether 125 patients (60 in the PPI arm and 65 in the standard care arm) who had undergone EST were analyzed. Immediate bleeding was noted in nine (15.0%) patients in the PPI group and four (6.2%) in the standard care group (P = 0.14). Overt delayed post-EST bleeding was seen in two (3.3%) and five (7.7%) patients in PPI and standard care arms, respectively (P = 0.44). There were no significant differences in other outcomes, including a decrease in hemoglobin of >20 g/L, the need for blood transfusion, length of hospital stay and 30-day mortality. CONCLUSION: Pre-emptive PPI did not reduce the risk of post-EST bleeding.

Real-life efficacy and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir in chronic hepatitis C patients in Hong Kong.

BACKGROUND AND AIM: In registration studies, combination therapy of paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) with and without ribavirin for 12-24 weeks can achieve > 90% sustained virological response (SVR) for genotype 1 hepatitis C virus (HCV) infection. However, data in Asia is scanty. We aimed to study the efficacy and safety of this combination therapy in chronic hepatitis C patients in Hong Kong. METHODS: We retrospectively analyzed data from six local hospitals that have prescribed PrOD with and without ribavirin to patients with genotype 1 chronic HCV infection as part of a global compassionate program. RESULTS: Among 41 patients treated, 35 (85%) patients had genotype 1b HCV infection, 6 (15%) had co-infection with human immunodeficiency virus, 35 (85%) failed previous peginterferon and ribavirin therapy, 25 (61%) had compensated liver cirrhosis, and 3 (7%) had liver transplantation. Thirty-five (85%) patients received 12-week treatment and six patients received 24-week treatment; 26 (63%) patients received ribavirin combination. Thirty-nine (95%; 95% confidence interval 88.5-100%) patients had undetectable HCV RNA at 12-week post-treatment, that is, SVR. The two patients who did not develop SVR discontinued treatment prematurely; both of them were treatment experienced with liver cirrhosis complicated by acute renal failure unrelated to the treatment of PrOD and ribavirin. No patient had hepatic decompensation. CONCLUSIONS: Paritaprevir/ritonavir, ombitasvir, and dasabuvir with or without ribavirin is effective and safe in patients with genotype 1 HCV infection in real-life clinical setting in Hong Kong.

To fine needle aspiration or not? An endosonographer's approach to pancreatic cystic lesions.

Endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) is an established diagnostic tool in the management of pancreatic cystic lesions (PCLs). Due to the proximity to the target lesion, the fine diagnostic needle travels through only minimal normal tissues. The risks of bleeding, pancreatitis and infection are small. Valuable diagnostic morphological information can be obtained by EUS before the use of FNA. The additional cytopathologic and cyst fluid analysis for the conventional markers such as amylase, carcinoembryonic antigen (CEA) and CA19.9 improves the diagnostic capability. Pancreatic cyst fluid CEA concentration of 192 ng/mL is generally the most agreed cutoff to differentiate mucinous from non-mucinous lesion. A fluid amylase level of <250 IU/L excludes the diagnosis of pseudocyst. Technical tips of EUS-FNA and the limitations of the procedure are discussed. Promising technique and FNA needle modifications have been described to improve the diagnostic yield at the cytopathologic analysis. The use of novel cyst fluid proteomics and deoxyribonucleic acid-based biomarkers of the PCLs are reviewed. Although it is considered a safe procedure, EUS-FNA is not a routine in every patient. Recommendations of the role of EUS-FNA at various common clinical scenarios are discussed.

Detection of colorectal adenoma by narrow band imaging (HQ190) vs. high-definition white light colonoscopy: a randomized controlled trial.

OBJECTIVES: The benefits of narrow band imaging (NBI) on enhancing colorectal adenoma detection remain questionable. We tested whether the new generation of NBI (190-NBI), which is twice as bright as the previous version, would improve adenoma detection when compared with high-definition white light (HD-WL) colonoscopy. METHODS: It was a randomized controlled trial with tandem colonoscopy. We recruited patients who underwent colonoscopy for symptoms, screening, or surveillance. Patients were randomized for the use of either 190-NBI or HD-WL on withdrawal. Tandem colonoscopy was performed by using the same assigned colonoscope and withdrawal method. Lesions detected on first-pass and second-pass examination were used for adenoma detection and miss rates, respectively. The primary outcomes were adenoma and polyp detection rates. RESULTS: A total of 360 patients were randomized to undergo either 190-NBI or HD-WL colonoscopy. Both the adenoma and polyp detection rates were significantly higher in the 190-NBI group compared with the HD-WL group (adenoma: 48.3% vs. 34.4%, P=0.01; polyps: 61.1% vs. 48.3%, P=0.02). The mean number of polyps detected per patient was higher in the 190-NBI group (1.49% vs. 1.13, P=0.07). There was no significant difference in the adenoma miss rates between the two groups (21.8% vs. 21.2%). Multivariate analysis showed that the use of 190-NBI (odds ratio (OR) 1.85; 95% confidence interval (CI) 1.10-3.12), withdrawal time (OR 1.29; CI 1.19-1.38), patient's age (OR 1.04; CI 1.01-1.06), and male gender (OR 2.38; CI 1.42-3.99) were associated with adenoma detection. CONCLUSIONS: 190-NBI colonoscopy was superior to the conventional HD-WL in detecting colorectal adenomas or polyps, but there was no significant difference in adenoma miss rates.

Ten day sequential versus 10 day modified bismuth quadruple therapy as empirical firstline and secondline treatment for Helicobacter pylori in Chinese patients: an open label, randomised, crossover trial.

OBJECTIVE: Treatments with sequential therapy (SEQ) or bismuth quadruple (QUAD) therapy have been proposed as empirical firstline regimens for Helicobacter pylori. We compared the efficacy and tolerability of 10 day SEQ with 10 day modified QUAD as both firstline and secondline treatments for H pylori in a randomised crossover study. DESIGN: H pylori positive and treatment naïve patients were randomly assigned to receive either 10 day SEQ (esomeprazole for 10 days, amoxicillin for an initial 5 days, followed by clarithromycin and metronidazole for a subsequent 5 days) or modified QUAD (esomeprazole, bismuth subcitrate, tetracycline and metronidazole). H pylori eradication was confirmed by urea breath test at 8 weeks. Patients who failed the initial assigned treatment were crossed over to receive the alternate regimen. The primary outcome was eradication rates of firstline treatment by intention to treat (ITT) and per protocol (PP) analyses. RESULTS: 357 patients were randomised to receive either SEQ or QUAD. The PP eradication rates of the SEQ and QUAD groups were 95.2% and 98.8%, respectively (p=0.10). Based on ITT analysis, the corresponding eradication rates were 89.4% and 92.7%, respectively (p=0.36). Eight (4.8%) patients in the SEQ and two (1.2%) patients in the QUAD who failed the firstline treatment were crossed over to the alternate regimen with 100% retreatment success. The overall incidence of adverse events was higher in the QUAD (16.7%) than in the SEQ (8.1%; p=0.032) group. CONCLUSIONS: Ten day sequential and modified bismuth quadruple therapies are both highly effective as empirical firstline therapies for H pylori in Chinese patients. CLINICALTRIALSGOV: NCT 01760824.

Prevalence of occult hepatitis B infection in a highly endemic area for chronic hepatitis B: a study of a large blood donor population.

BACKGROUND AND AIMS: The aim of the present study was to determine the population prevalence of occult hepatitis B (OHB) infection and its clinical profile in a highly endemic area of chronic hepatitis B virus disease. METHODS: OHB was first identified by individual sample testing for hepatitis B surface antigen (HBsAg) followed by nucleic acid testing (NAT) and vice versa for 3044 (cohort 1, stored sera from donation within 1 year) and 9990 (cohort 2, prospective study) blood donors, respectively. OHB was confirmed meticulously by ≥2 out of 3 tests with detectable hepatitis B virus (HBV) DNA using a sensitive standardised assay. Detailed serology and viral load in the serum and liver were studied. RESULTS: The prevalence of OHB was 0.13% (4/3044) and 0.11% (11/9967) for cohort 1 and 2, respectively. In cohort 2, 10 out of 11 OHB samples were positive for anti-HBc (hepatitis B core antigen) antibody (all were immunoglobulin G). Seven had detectable anti-HBs. The serum HBV DNA levels were extremely low (highest 14.1 IU/ml). Of the six donors who underwent liver biopsies, all had normal liver biochemistry, extremely low liver HBV DNA (highest 6.21 copies/cell) and nearly normal liver histology. For those with viral sequence generation, none had the common HBsAg mutant G145R. CONCLUSIONS: The prevalence of OHB in a highly endemic area of chronic HBV was very low, thus implying a low impact on transfusion services. To implement universal screening, the high cost of NAT should be taken into account. OHB blood donors had very low HBV replication, and normal liver biochemistry and histology, conferring a favourable prognosis.

Safety evaluation of telbivudine.

IMPORTANCE OF THE FIELD: Successful treatment of chronic hepatitis B (CHB) often requires long-term oral nucleoside/nucleotide agents which can be associated with viral resistance, patient non-compliance and adverse effects. Telbivudine is one of the more potent options available, with a 6.5- to 6.6-log copies/ml hepatitis B DNA reduction at 12 weeks in an early viral kinetic study, a potency comparable to entecavir. It is also one of the few drugs in the treatment of CHB under FDA pregnancy Category B. AREAS COVERED IN THIS REVIEW: The efficacy and safety profile of telbivudine in compensated and decompensated CHB patients compared to other agents are discussed. Viral resistance, characteristic adverse effects including elevation in creatine kinase and peripheral neuropathy in telbivudine treatment are reviewed. Infrequent but significant adverse effects of other nucleoside/nucleotide analogs are highlighted. WHAT THE READER WILL GAIN: Readers are provided the latest update on the clinical profile of long-term use of telbivudine. TAKE HOME MESSAGE: Long-term telbivudine treatment offers effective viral suppression to CHB patients with certain baseline characteristics and on-treatment virologic response. Creatine kinase elevation is not a good predictor of muscle-related adverse effects with nucleoside/nucleotide analogs. But significant myopathy and neuropathy have been reported in a small number of patients receiving telbivudine.

Reduction of liver stiffness following resolution of acute flares of chronic hepatitis B.

BACKGROUND: Measuring liver stiffness is becoming more popular as a non-invasive tool for assessing liver fibrosis. AIM: To assess the effect of severe hepatitis B flare on liver stiffness and determine factors that correlate with liver stiffness measurements. METHODS: Twenty-nine patients with severe hepatitis B flare (ALT > 10 × upper limit of normal) were followed up for 1 year. Serial transient elastography was performed at the time of flare, 3-6, and 12 months after flare. RESULTS: At the time of flare, the median liver stiffness was 16.8 kPa, with no patients having normal liver stiffness (<6 kPa). There was a significant decrease in liver stiffness from baseline to 3-6 months (16.8 vs. 7.9 kPa, respectively, P < 0.001), and a further smaller decline from 3-6 to 12 months (7.9 vs. 6.9 kPa, respectively, P = 0.039). By 12 months, 10 (34%) had normalized their liver stiffness. Baseline parameters which correlated with liver stiffness include bilirubin, ALT, albumin, prothrombin time and platelet levels (all P < 0.05). CONCLUSION: Liver stiffness was increased in patients with severe hepatitis B flares, with return to near normal levels by 6 months. Transient elastography for proper assessment of liver fibrosis should be performed at least 6 months after flare.

Correlation of liver stiffness and histological features in healthy persons and in patients with occult hepatitis B, chronic active hepatitis B, or hepatitis B cirrhosis.

OBJECTIVES: Liver stiffness measurement using transient elastography has become a popular tool to assess liver fibrosis. The aim of this study was to determine liver stiffness values and histological features in healthy subjects and in patients with chronic hepatitis B (CHB). METHODS: A total of 157 people were included (28 healthy subjects and 18 patients with occult hepatitis B infection, 102 with active CHB, and 9 with end-stage hepatitis B cirrhosis). Histology and liver stiffness measurements were obtained from all patients. RESULTS: The median liver stiffness in healthy subjects and in occult hepatitis B, active hepatitis B, and end-stage cirrhosis patients was 4.6, 4.2, 8.7, and 33.8 kPa, respectively. In healthy subjects and in patients with occult hepatitis B infection, none had significant fibrosis on histology, and all had liver stiffness <7.2 kPa. In patients with active CHB, 32 (31%) had liver stiffness >11.0 kPa, but only four (12%) had cirrhosis on histology. Using liver stiffness to predict cirrhosis in this group had a sensitivity of 100%, a specificity of 69%, a positive predictive value of 10%, and a negative predictive value of 100%. All nine patients with end-stage liver cirrhosis had liver stiffness >11.0 kPa. The overall area under the ROC curve (AUROC) for diagnosing cirrhosis using a cutoff of 11.3 kPa was 0.89. CONCLUSIONS: Liver stiffness measurement has an overall good diagnostic accuracy with excellent negative predictive value. However, in active CHB with elevated alanine aminotransferase (ALT) levels, the positive predictive value for diagnosing cirrhosis is poor, and further studies are needed to optimize the use of transient elastography in this important group.

Clarithromycin-amoxycillin-containing triple therapy: a valid empirical first-line treatment for Helicobacter pylori eradication in Hong Kong?

BACKGROUND: Recent studies have suggested the eradication rate for Helicobacter pylori infection with standard amoxycillin-clarithromycin-containing triple therapy as first-line treatment have fallen below 80%. Levofloxacin-containing triple therapy was proposed as an alternative. The aim of this study is to compare the efficacy and tolerability of the standard 7-day clarithromycin-containing triple therapy against the 7-day levofloxacin-containing triple therapy, and to assess whether the classical triple therapy is still valid as empirical first-line treatment for H. pylori infection in Hong Kong. METHODS: Three hundred consecutive H. pylori-positive patients were randomized to receive either 1 week of EAL (esomeprazole 20 mg b.d., amoxycillin 1 g b.d., and levofloxacin 500 mg daily) or EAC (esomeprazole 20 mg b.d., amoxycillin 1 g b.d., and clarithromycin 500 mg b.d.). H. pylori status was rechecked by (13)C-urea breath test 6 weeks after treatment. Patients who failed either of the first-line eradication therapy were invited to undergo H. pylori susceptibility testing. RESULTS: H. pylori eradication was achieved in 128 of 150 (85.3%) patients in EAL and 139 of 150 (92.7%) patients in EAC groups, respectively (p = .043), for both intention-to-treat and per-protocol analysis. More patients in the clarithromycin- than the levofloxacin-containing therapy group developed side effects from the medication (21.3% vs 13.3%, p = .060). Nine patients (six from the EAL group and three from the EAC group) who failed their corresponding eradication therapy returned for susceptibility testing. All nine isolates were highly resistant to levofloxacin (minimum inhibitory concentration or MIC > 32 microg/mL), whereas only two of the six isolates from the EAL group were resistant to clarithromycin (MIC > 0.5 microg/mL). CONCLUSIONS: The standard 7-day clarithromycin-containing triple therapy is still valid as the most effective empirical first-line eradication therapy for H. pylori infection in Hong Kong, as prevalence of primary resistance of H. pylori to amoxycillin and clarithromycin remains low. Patients who failed their empirical first-line eradication therapy should undergo H. pylori susceptibility testing to guide further treatment.

Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B.

BACKGROUND/AIMS: To determine whether gender, age, hepatitis B virus genotype, core promoter and precore mutations, HBeAg/ anti-HBe status, HBV DNA, ALT levels and cirrhosis on presentation were independent risk factors and derive a novel risk score for the development of HCC. METHODS: CHB patients (820) were followed up (mean duration 76.8 months) for the occurrence of HCC. RESULTS: The 5- and 10-year prevalence of HCC were 4.4% and 6.3%, respectively. Cox regression analysis showed that male gender (p = 0.025, RR 2.98), increasing age (p < 0.001, RR 1.07), higher HBV DNA levels (p = 0.02, RR 1.28), core promoter mutations (p = 0.007, RR 3.66), and presence of cirrhosis (p < 0.001, RR 7.31) were independent risks for the development of HCC. A risk score was derived and validated with sensitivity > 84% and specificity > 76% to predict the 5- and 10- year risks for the development of HCC. The AUC for the 5- and 10-year prediction were 0.88 and 0.89, respectively. CONCLUSIONS: The risk score, based on age, gender, HBV DNA levels, core promoter mutations and cirrhosis, can estimate the chance of development of HCC in 5 and 10 years after presentation. It can be used to identify high-risk CHB patients for treatment and screening of HCC.

Factors affecting physicians' practices related to Helicobacter pylori infection: effect of experience and mode of practice.

BACKGROUND: Studies found that guidelines on the management of Helicobacter pylori were not always followed in clinical practice. This study investigated factors that were responsible for the deviation. METHODS: A cross-sectional survey using a structured self-administered questionnaire was used to ask physicians whether they would offer testing and treatment for H. pylori infection in different clinical scenarios. RESULTS: 170 medical practitioners completed the questionnaires. Respondents in the private sector were significantly more likely to test and treat than those in the public sector for patients with a history of peptic ulcer, gastric cancer or no symptom (p = 0.018, <0.001 and 0.041, respectively). Significant differences in practice were noted amongst practitioners of different specialty and seniority, but not qualification. Medical practitioners in the private sector complied with the guidelines significantly better than those in the public sector (p = 0.002) and so did senior practitioners compared with junior practitioners (p < 0.001). The specialty and qualification of the respondents, however, did not have a significant effect. CONCLUSION: There were significant differences in the management of H. pylori amongst medical practitioners from the private and public sectors and amongst senior and junior practitioners. Published guidelines were not completely followed. Further educational campaigns are needed.

Twenty-two years follow-up of a prospective randomized trial of hepatitis B vaccines without booster dose in children: final report.

Long-term immunogenicity and efficacy of HBVvaccination with different regimens of HBV vaccines (A: 2-dose recombinant vs. B: 3-dose recombinant vs. C: 3-dose plasma-derived vaccines) without booster dose were examined in 318 Chinese children. Geometric mean titer (GMTs) of anti-HBs of group A subjects was significantly lower than that of groups B and C subjects at years 1, 5, 10 and 15. At year 22, the proportion of subjects with anti-HBs > or = 10 mlU/mL for groups A, B and C were 35.3%, 76.5% and 52.4%, respectively (p < 0.05 between groups A and B) in 55 subjects. In the 22 years study period, none was found to be HBsAg positive, and 72 subjects had > or = 1 episodes of anamnestic response. In conclusion, the 3-dose regimens have a better long-term immunogenicity. In terms of protection against HBV infection, the 2-dose and 3-dose vaccines had equal efficacies.

HBsAg Seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma.

BACKGROUND & AIMS: Our aims were to study the virologic, histologic, and clinical outcome in chronic hepatitis B (CHB) patients with hepatitis B surface antigen (HBsAg) seroclearance. METHODS: We determined the age of HBsAg seroclearance that is associated with a lower risk for hepatocellular carcinoma (HCC) in 298 CHB patients (median follow-up, 108 months). The following virologic and histologic features were also determined: liver stiffness (n = 229), liver histology, serum HBV DNA levels over time (n = 265), intrahepatic HBV DNA with covalently closed circular DNA (cccDNA) levels, and messenger RNA (mRNA) expression. RESULTS: The median age of HBsAg seroclearance was 49.6 years. Seven (2.4%) patients developed HCC. Cumulative risk for HCC was higher in patients with HBsAg seroclearance at ages >or=50 years compared with those with HBsAg seroclearance at ages <50 (P = .004) years. Of these 2 groups of patients, 29.5% and 7.9%, respectively, had significant fibrosis by liver stiffness measurement (P = .001), and 15.4% of patients had mild histologic fibrosis. Intrahepatic total HBV DNA and cccDNA were detected in 100% and 79.3% of patients, respectively. All patients had undetectable surface and precore/pregenomic RNA transcripts. One (9.1%) patient had X mRNA expression. Serum HBV DNA were detectable in 13.4%, 6.1%, and 3.7% of patients within 1 year and 5-10 and >10 years after HBsAg seroclearance, respectively, and 82.1% patients had persistently normal alanine aminotransferase levels. CONCLUSIONS: HBV persisted at low replicative and transcriptional levels after HBsAg seroclearance. HBsAg seroclearance at age <50 years was associated with a lower risk for the development of HCC.

Prevalence of fibrosis and cirrhosis in chronic hepatitis B: implications for treatment and management.

OBJECTIVE: To document the prevalence and factors associated with severe fibrosis and cirrhosis in a large population of Asian chronic hepatitis B (CHB) patients. METHODS: Transient elastography was performed in unselected CHB patients. Liver stiffness score of <8.1 kPa was used as a cut-off for the presence of severe fibrosis or liver cirrhosis. RESULTS: 1315 patients were recruited, of which 951 (72%) were treatment-naive. Of these, 319 (34%) had severe fibrosis, with higher prevalence seen in males compared with females (39% vs 24% respectively, p < 0.01. Severe fibrosis was seen with increasing age from 20% in patients <25 years to 81% in those >65 years. Higher prevalence of severe fibrosis was seen in HBeAg(+) patients compared to HBeAg(-) patients age >45 years (58% vs 43% respectively, p = 0.03), in patients with HBV DNA levels >or=4 log compared with <4 log copies/ml (41% vs 27% respectively, p < 0.01), and in patients with stepwise increase of ALT levels (<0.5 x ULN vs 0.5-1 x ULN vs 1-2 x ULN; 11% vs 30% vs 48% respectively, p < 0.01). After multivariate analysis, gender, age and ALT levels were significant factors associated with severe fibrosis. Patients who received antiviral treatment had lower ALT, stiffness score and prevalence of cirrhosis compared to treatment-naive patients [25 vs 35 U/L (p < 0.01), 6.2 vs 6.7 kPa (p = 0.031) and 14% vs 22% (p = 0.008) respectively]. CONCLUSION: The overall prevalence of severe fibrosis in CHB patients was 34% with higher rates seen in older age groups, males, and in patients with higher ALT levels.

Natural history of hepatitis-related hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is an important cause of cancer death in the world. It has great regional differences in the pathology and epidemiology. The variation is greatly influenced by the aetiologies of the disease. Hepatitis B and C infection are the most important risk factors. HCC incidence rates are higher but in decreasing trend in developing countries. However, the figures in the developed countries are contrary. Successful hepatitis B virus (HBV) vaccination programs, better food hygiene, increased global hepatitis C virus (HCV) prevalence and population migration are the possible explanations. A number of clinical and pathogenic differences exist between HBV- and HCV-related HCC. HBV infection leads to the development of HCC through direct and indirect pathways as it has the ability to integrate into the host genome affecting cellular signaling and growth control. HCV causes HCC mainly through indirect pathways: chronic inflammation, cell deaths and proliferation. As a result, HCC is almost exclusively found in cirrhotic HCV patients while HCC is sometimes found in HBV patients without significant liver cirrhosis. Due to the different severities of liver cirrhosis and HCC extent, therapeutic strategies from resection, liver transplantation to symptoms palliation are available. Poorly differentiated histology, lack of fibrous capsule, large tumour size, early vascular invasion and elevated serum levels of alpha fetoprotein (AFP) are the features for more aggressive disease. Combined with markers of liver reserve and performance status, accurate scoring systems and models have been developed to predict patients' survival and match best treatment option.