Efficacy of entecavir in chronic hepatitis B patients with mildly elevated alanine aminotransferase and biopsy-proven histological damage.

UNLABELLED: Current guidelines for management of chronic hepatitis B recommend treatment for patients presenting with elevated hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) >2 x upper limit of normal (ULN) or histological evidence of liver disease. Retrospective analyses have demonstrated that significant hepatic necroinflammation and fibrosis were present in a substantial proportion of patients with ALT 1 to 2 x ULN. To assess therapeutic efficacy in this clinical setting, we retrospectively examined treatment endpoints among the subset of nucleoside-naïve chronic hepatitis B (CHB) patients treated in phase 3 clinical trials of entecavir who had both screening and baseline serum ALT 1.3 to 2 x ULN. A total of 1347 patients were randomized to treatment with entecavir or lamivudine. Three hundred thirty-six patients, constituting 25% of the total study population, had screening and baseline ALT 1.3 to 2 x ULN. Clinically significant necroinflammation (Knodell necroinflammation score > or =7) was observed in 60% and 72% of hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients, respectively, whereas marked fibrosis (Ishak fibrosis score > or =4) was observed in 8% and 15% of HBeAg-positive and HBeAg-negative patients, respectively. Among entecavir-treated HBeAg-negative patients, the proportions of patients achieving histological improvement, HBV DNA <300 copies/mL, and ALT normalization were similar between patients with mildly elevated ALT and those with ALT >2 x ULN. However, entecavir-treated HBeAg-positive patients with mildly elevated ALT had lower response rates for histological improvement, HBV DNA less than 300 copies/mL, ALT normalization, and HBeAg seroconversion than those with ALT greater than 2 x ULN. CONCLUSION: This retrospective analysis demonstrated that HBeAg-negative CHB patients treated with entecavir responded similarly irrespective of baseline ALT level. However, HBeAg-positive patients with mildly elevated ALT responded less well to treatment with entecavir than did those with ALT greater than 2 x ULN.

Insulin resistance is independently associated with significant hepatic fibrosis in Asian chronic hepatitis C genotype 2 or 3 patients.

BACKGROUND AND AIM: The role of insulin resistance (IR) and hepatic steatosis in fibrogenesis in chronic hepatitis C infection (CHC) has yielded conflicting data and few studies have been performed in Asian-region populations. We retrospectively investigated the relationship between host metabolic variables, including IR and hepatic steatosis, to hepatic fibrosis in Asian-region CHC genotype 2/3 patients. METHODS: A total of 303 treatment-naïve Asian-region patients with CHC genotype 2/3 were enrolled in a multicenter phase 3 study of albinterferon alfa-2b plus ribavirin for 24 weeks. IR was defined as Homeostasis Model for Assessment of IR (HOMA-IR) > 2. Baseline liver biopsy was evaluated by a single expert histopathologist. Post hoc subgroup logistic regression modeling selected for independent variables associated with significant fibrosis (METAVIR stage F2-F4). RESULTS: Insulin resistance was available in 263 non-diabetic Asian-region patients (hepatitis C virus-2 [HCV-2] = 171, HCV-3 = 92), and 433 non-Asian region patients (407 "Caucasian"); METAVIR fibrosis prevalence F0-F1 (minimal fibrosis)= 201 (77%) and F2-F4 (significant fibrosis) = 59 (23%), and steatosis prevalence of grade 0 = 169 (65%), grade 1 = 64 (25%), grade 2/3 = 27 (10%). Median HOMA-IR was 1.8 (interquartile range: 1.2-2.7); 100 (38%) patients had HOMA-IR > 2. Factors independently associated with significant fibrosis included HOMA-IR (odds ratio [OR]= 8.42), necro-inflammatory grade (OR = 3.17), age (OR = 1.07) and serum total cholesterol levels (OR = 0.008). This was similar to non-Asian region patients, but steatosis was not associated with significant fibrosis in either cohort. CONCLUSIONS: In this subgroup study of Asian-region HCV genotype 2 or 3 patients, insulin resistance, along with age, cholesterol levels and necro-inflammation, but not steatosis may be associated with significant hepatic fibrosis.

Gallbladder wall thickening in patients with acute hepatitis.

BACKGROUND: Gallbladder wall thickening (GWT) is often observed in patients with acute hepatitis (AH). However, little is known regarding the relationship between AH and GWT. We analyzed the characteristics of GWT in patients with AH. METHOD: Between April 2002 and April 2007, 232 patients with AH underwent a sonographic examination. The clinical and laboratory findings of patients with GWT were evaluated and compared with patients without GWT. Data were recorded for the following variables: gender, age, laboratory findings, duration of symptom, presence of gallstone, and etiology of GWT. RESULTS: A total of 147 (63%) patients with AH had GWT. GWT in patients with an alanine aminotransferase level more than 500 IU/l (5.2 +/- 3.4 mm) was greater than that in other patients (3.9 +/- 2.3 mm; p < 0.05). Hepatitis A virus infection (odds ratio = 3.17 [1.42-7.09]), female gender (odds ratio = 2.47 [1.34-4.56]), and an elevated total bilirubin level (odds ratio = 1.09 [1.03-1.15]) were positively associated with GWT. CONCLUSION: The incidence of GWT in patients with AH was 63%, and there was an association with hepatitis A virus infection, female gender, and an elevated total bilirubin level.

Symptom experience in Korean patients with liver cirrhosis.

This study was done to examine the level of symptom experience, and symptom variation in relation to demographic and clinical variables, in Korean patients with liver cirrhosis (LC). Symptom experience was measured using a scale developed by the researchers through a literature review on LC. Participants were 129 patients whose mean age was 53.6 (standard deviation [SD] = 9.28) years. The results indicated that (1) overall symptom experience was relatively low (mean 41.67, SD 24.71); (2) the main symptoms needing a management were fatigue, abdominal distension and/or peripheral edema, and muscle cramps; and (3) among the study variables, the severity of LC (P < 0.001) and the number of hospitalizations (P = 0.014) showed a significant relationship with overall symptom experience. These results suggest that symptom assessment requires a multidimensional approach and that it is imperative to consider disease severity in developing tailored symptom management programs for Korean patients with LC.

Primary liver carcinoma of intermediate (hepatocyte-cholangiocyte) phenotype.

BACKGROUND/AIMS: Recent evidence of hepatic progenitor cells with the bipotential to differentiate into hepatocytes and cholangiocytes gives rise to the suggestion that primary hepatic carcinomas with features intermediate between hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) may originate from hepatic progenitor cells. METHODS: Fifty-four cases of primary liver carcinomas were selected and an immunohistochemical analysis was performed using hepatocytic markers (alpha-fetoprotein, hepatocyte), cholangiocytic markers (carcinoembryonic antigen, cytokeratin 19) and progenitor cell marker (c-kit). RESULTS: Thirteen cases designated 'intermediate' carcinomas demonstrated strands/trabeculae of small, uniform, round-to-oval cells with scanty cytoplasm and hyperchromatic nuclei embedded within a thick desmoplastic stroma. Six were designated transitional type combined hepatocellular-cholangiocarcinoma (CHC). Ten were named HCC small cell type, demonstrating similar features to typical HCC, but composed of smaller cells. Simultaneous expression of hepatocytic and cholangiocytic markers was demonstrated in 8/13 (61.5%), 4/6 (66.7%), and 3/10 (30%) cases of intermediate carcinomas, transitional CHCs, and HCC small cell type, respectively, and c-kit expression was noted in 10/13 (76.9%), 4/6 (66.7%) and 7/10 (70%) cases, in the same order. CONCLUSIONS: Intermediate carcinoma may be a distinct type of primary liver carcinoma, morphologically and phenotypically intermediate between HCC and CC, which originates from transformed hepatic progenitor cells.