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.

Sustained disease remission after spontaneous HBeAg seroconversion is associated with reduction in fibrosis progression in chronic hepatitis B Chinese patients.

UNLABELLED: Recently, controversies have arisen about whether hepatitis B e antigen (HBeAg) seroconversion can result in regression of fibrosis, thus improving the clinical outcome of Chinese patients with chronic hepatitis B. In this study, we determined if spontaneous HBeAg seroconversion is associated with regression of fibrosis in Chinese chronic hepatitis B patients. We evaluated the histology of liver samples from 128 HBeAg-positive treatment-naive Chinese patients who had undergone 2 liver biopsies over the years. Regression of fibrosis was defined as a decrease in fibrosis stage of at least 1 point. Sustained disease remission was defined as HBeAg seroconversion and hepatitis B virus (HBV) DNA < 10(4) copies/ml at follow-up liver biopsy. The mean duration (+/- standard error of the mean) between the initial and follow-up liver biopsies was 43.9 +/- 3.4 months. Regression of fibrosis was higher in patients with sustained disease remission (5 of 13 [38.5%] versus 22 of 115 [19.1%], P < 0.00005), patients who were younger (20-29 years old) at initial liver biopsy (17 of 54 [31.5%] versus 10 of 74 [13.5%], P = 0.0004), and patients with genotype B (17 of 43 [39.5%] versus 10 of 85 [11.8%], P = 0.004). On multivariate analysis, sustained disease remission (relative risk [RR] 3.00, 95% confidence interval [95% CI] 1.29-7.01, P = 0.01) and being 20-29 years old at initial liver biopsy (RR 2.94, 95% CI 1.01-8.62, P = 0.04) were independently associated with regression of fibrosis. The rate of fibrosis progression was lower in patients with sustained disease remission than in those who remained HBeAg positive (median 0 fibrosis units/year, range -2.00 to -0.70 fibrosis units/year, versus median 0.51 fibrosis units/year, range 0 to +2.03 fibrosis units/year, P = 0.02). CONCLUSION: Spontaneous sustained remission of disease is associated not only with little progression of fibrosis but also with regression of fibrosis.

Instability of clonality in gastric lymphoid infiltrates: a study with emphasis on serial biopsies.

The evolution of low-grade B-cell mucosa-associated lymphoid-tissue (MALT) lymphoma of the stomach is a multistage process, reflected in the histologic continuum from Helicobacter pylori-chronic gastritis, to low-grade and high-grade lymphoma. Interestingly, in daily gastric biopsy sign-out, the authors observed that some biopsies showed monoclonality on polymerase chain reaction (PCR) even though there were no definite histologic features of malignancy and vice versa. To address the question, the authors studied the endoscopic gastric biopsies at first presentation of 46 patients to examine any clonality differences among various histologic patterns within the spectrum of MALT lymphoma evolution. The gastric biopsies were reviewed histologically and graded according to the Wotherspoon-Isaacson histologic scoring system from grade 0 (normal) to grade 5 (MALT lymphoma). The clonality of cases in each grade was determined by performing nested PCR for immunoglobulin heavy chain (IgH) gene rearrangement using FR2/JH and FR3/JH primer sets. The monoclonality rates among different grades were as follows: grade 2, 6.3% (1 of 16); grade 3, 27.3% (3 of 11); grade 4, 83.3% (5 of 6); grade 5, 69.2% (9 of 13). Statistically significant difference of monoclonality rate is demonstrated in histologic grade 4 versus grades 2 and 3, and grade 5 versus grade 2 (P < 0.05, Fisher exact test). The authors went on to examine the progress of disease by following up the clinical status, histologic changes, and clonality fluctuation of these cases. Four of the 8 patients with monoclonality on PCR, but no definite lymphoma at first presentation later progressed to frank MALT lymphoma. Our study shows that, during the progression to MALT lymphoma, there is an instability of clonality. Clonality can fluctuate between polyclonality, oligoclonality, and monoclonality, none of which defines an irreversible stage for progression to MALT lymphoma. Monoclonality is a risk factor for development of MALT lymphoma. Those cases with dense gastric mucosal lymphoid infiltrate (without definite MALT lymphoma) and monoclonality on PCR need to be closely monitored and Helicobacter infection promptly treated if present. In combination with clinicohistologic examination, PCR can serve as a complementary tool in arriving at a definite diagnosis of MALT lymphoma in cases with borderline histologic features.