Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using liver stiffness measurement (FibroScan®)

Dept. of Medicine/석사Background/ Aims: Liver stiffness measurement (LSM) using FibroScan® accurately assesses the degree of liver fibrosis and the risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C (CHC). This study investigated the usefulness of LSM as a predictor of HCC development in patients with chronic hepatitis B (CHB).Methods: A total of 1,130 patients with non-biopsy proven CHB who underwent LSM between May 2005 and December 2007 were enrolled in this prospective study. After LSM was performed, patients attended regular follow-up as part of a surveillance program for the detection of HCC.Results: The mean age of the patients (767 men, 363 women) was 50.2 years and the median LSM was 7.7 kPa. Six hundred seventy two (59.5%) patients received antiviral treatment before or after enrollment. During the follow-up period (median, 30.7 months; range 24.0-50.9 months), HCC developed in 57 patients (2.0% per 1 person-year). The 1, 2, and 3-year cumulative incidence rates of HCC were 0.80%, 3.26%, and 5.98%, respectively. On multivariate analysis, together with old age, male gender, heavy alcohol consumption (> 80 g/day), serum albumin, and hepatitis B e antigen positivity, patients with a higher LSM value were at a significantly greater risk of HCC development, with a hazard ratio of 3.07 [95% CI, 1.01–9.31; P=0.047] when LSM value 8.1–13 kPa, 4.68 [95% CI, 1.40–15.64; P=0.012] when LSM value 13.1–18 kPa, 5.55 [95% CI, 1.53–20.04; P=0.009] when LSM value 18.1–23 kPa, and 6.60 [95% CI, 1.83–23.84; P=0.004] when LSM value >23 kPa, as compared to LSM value ≤8 kPa.Conclusion: Our data suggest that LSM could be a useful predictor of HCC development in patients with CHB.ope

Preventive effect of empagliflozin and ezetimibe on hepatic steatosis in adults and murine models

Background: Even though many oral glucose-lowering or lipid-lowering agents have already been reported to improve hepatic steatosis to some degree, which drug had a more beneficial effect on hepatic steatosis among those drugs has not been precisely explored. We analysed the effect of empagliflozi, a selective sodium-glucose cotransporter 2 inhibitor, and ezetimibe on developing hepatic steatosis. Methods and results: Using 4005,779 patients with type 2 diabetes mellitus (T2DM) or dyslipidemia provided by the Korean National Health Insurance Service (NHIS) between January 2015 and December 2015, we analyzed the odds ratio (OR) of fatty liver development (fatty liver index [FLI] >60). Additionally, we examined the metabolic effects of ezetimibe and empagliflozin in mice fed with a choline-deficient high-fat diet, mimicking the features of human NAFLD. The experiment for agents was performed for the non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) mouse models independently. In the NHIS data, ORs for the development of fatty liver were significantly lower in all treatment groups than in the reference group, which did not receive ezetimibe or empagliflozin. (Ezetimibe therapy; OR=0.962, empagliflozin therapy; OR=0.527, ezetimibe plus empagliflozin; OR=0.509 compared to reference therapy). Unlike non-alcoholic steatohepatitis mouse model, ezetimibe, empagliflozin, and combination therapy also reduced liver steatosis in the non-alcoholic fatty liver mouse model. Conclusions: Compared with other agents, empagliflozin and/or ezetimibe treatment reduced the risk of developing hepatic steatosis. Our data suggest that empagliflozin or ezetimibe can be primarily considered in type 2 DM or dyslipidemia patients to prevent hepatic steatosis.ope

Treatment of Chronic Hepatitis C Using Newly Developed Oral Antiviral Agents

Standard care for chronic hepatitis C has been a combination of pegylated interferon-alpha and ribavirin, although this treatment has suboptimal antiviral efficacy and significant adverse events. The hepatitis C virus treatment landscape has been transformed recently by the development of direct-acting antiviral agents (DAAs) that target NS3 protease, NS5A protein, and NS5B polymerase. Several DAAs showed potent antiviral activity leading to increased rates of sustained virological response (SVR), even in difficult-to-treat patients such as older patients and those with advanced liver disease and prior failed peg-interferon/ribavirin treatment. Use of multiple DAAs without pegylated interferon has shown dramatically high SVR rates (up to nearly 100%) with negligible side effects. Interferon-free regimens are close to becoming the new standard of care for patients with chronic hepatitis C in USA and Europe. Similarly, several DAAs are near clinical use in Korea. This review discusses DAAs that have been approved or are under investigation for approval in Koreaope

A case of isolated metastatic hepatocellular carcinoma arising from the pelvic bone

Reports of metastatic hepatocellular carcinoma (HCC) without a primary liver tumor are rare. Here we present a case of isolated HCC that had metastasized to the pelvic bone without a primary focus. A 73-year-old man presented with severe back and right-leg pain. Radiological examinations, including computed tomography (CT) and magnetic resonance imaging (MRI), revealed a huge mass on the pelvic bone (13×10 cm). He underwent an incisional biopsy, and the results of the subsequent histological examination were consistent with metastatic hepatocellular carcinoma. The tumor cells were positive for cytokeratin (AE1/AE3), hepatocyte paraffin 1, and glypican-3, and negative for CD56, chromogranin A, and synaptophysin on immunohistochemical staining. Examination of the liver by CT, MRI, positron-emission tomography scan, and angiography produced no evidence of a primary tumor. Radiotherapy and transarterial chemoembolization were performed on the pelvic bone, followed by systemic chemotherapy. These combination treatments resulted in tumor regression with necrotic changes. However, multiple lung metastases developed 1 year after the treatment, and the patient was treated with additional systemic chemotherapyope

The relationship between visceral obesity and hepatic steatosis measured by controlled attenuation parameter.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is closely related with obesity. However, obese subjects, generally represented by high BMI, do not always develop NAFLD. A number of possible causes of NAFLD have been studied, but the exact mechanism has not yet been elucidated. METHODS: A total of 304 consecutive subjects who underwent general health examinations including abdominal ultrasonography, transient elastography and abdominal fat computed tomography were prospectively enrolled. Significant steatosis was diagnosed by ultrasonography and controlled attenuation parameter (CAP) assessed by transient elastography. RESULTS: Visceral fat area (VFA) was significantly related to hepatic steatosis assessed by CAP, whereas body mass index (BMI) was related to CAP only in univariate analysis. In multiple logistic regression analysis, VFA (odds ratio [OR], 1.010; 95% confidence interval [CI], 1.001-1.019; P = 0.028) and triglycerides (TG) (OR, 1.006; 95% CI, 1.001-1.011; P = 0.022) were independent risk factors for significant hepatic steatosis. The risk of significant hepatic steatosis was higher in patients with higher VFA: the OR was 4.838 (P200 cm2, compared to patients with a VFA ≤100 cm2. CONCLUSIONS: Our data demonstrated that VFA and TG is significantly related to hepatic steatosis assessed by CAP not BMI. This finding suggests that surveillance for subjects with NAFLD should incorporate an indicator of visceral obesity, and not simply rely on BMI.ope

Synchronous development of intrahepatic cholangiocarcinoma and hepatocellular carcinoma in different sites of the liver with chronic B-viral hepatitis: two case reports

BACKGROUND: Synchronous development of primary hepatocellular carcinoma and intrahepatic cholangiocarcinoma has been reported rarely. In literature review, there have been only 35 reported cases of synchronous hepatocellular carcinoma and intrahepatic cholangiocarcinoma, and most of these tumors developed in patients with hepatitis C-related liver cirrhosis. Here, we present synchronous development of hepatocellular carcinoma and intrahepatic cholangiocarcinoma in two patients with chronic B-viral hepatitis. CASE PRESENTATION: Two patients with chronic hepatitis B were referred to our hospital due to a hepatic mass. Patient 1 had a 6.4 cm multinodular hepatic mass in the left lobe and a small nodule in the right lobe. Patient 2 had a 4.3 cm hypervascular mass in the right lobe and a 1.1 cm nodule in the left lobe. The pre-operative diagnosis of both cases was hepatocellular carcinoma with metastatic nodule, however, surgical resection pathology revealed that hepatocellular carcinoma and intrahepatic cholangiocarcinoma existed independently in the other side of the liver in both cases. Additionally, the background liver histology of both cases was hepatitis B-related chronic hepatitis without cirrhotic change. CONCLUSION: Our cases suggest that hepatitis B virus infection can also predispose to development of double liver cancers.ope

Prediction of liver-related events using fibroscan in chronic hepatitis B patients showing advanced liver fibrosis

BACKGROUND: Liver stiffness measurement (LSM) using transient elastography (FibroScan®) can assess liver fibrosis noninvasively. This study investigated whether LSM can predict the development of liver-related events (LREs) in chronic hepatitis B (CHB) patients showing histologically advanced liver fibrosis. METHODS: Between March 2006 and April 2010, 128 CHB patients with who underwent LSM and liver biopsy (LB) before starting nucleot(s)ide analogues and showed histologically advanced fibrosis (≥F3) with a high viral loads [HBV DNA ≥2,000 IU/mL] were enrolled. All patients were followed regularly to detect LRE development, including hepatic decompensation (variceal bleeding, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome) and hepatocellular carcinoma (HCC). RESULTS: The mean age of the patient (72 men, 56 women) was 52.2 years. During the median follow-up period [median 27.8 (12.6-61.6) months], LREs developed in 19 (14.8%) patients (five with hepatic decompensation, 13 with HCC, one with both). Together with age, multivariate analysis identified LSM as an independent predictor of LRE development [P19 kPa were at significantly greater risk than those with LSM≤19 kPa for LRE development (HR, 7.176; 95% CI, 2.257-22.812; P = 0.001). CONCLUSION: LSM can be a useful predictor of LRE development in CHB patients showing histologically advanced liver fibrosis.ope

Association Between Heme Oxygenase-1 Promoter Polymorphisms and the Development of Albuminuria in Type 2 Diabetes: A Case?Control Study

Heme oxygenase (HO)-1 is a key enzyme in cytoprotective mechanisms against oxidative stress in the cardiovascular-renal system. The T(-413)A single nucleotide polymorphism (SNP) and (GT)n microsatellite polymorphism in the HO-1 gene promoter modulate the HO-1 gene transcriptional activity and these polymorphisms are associated with various human diseases.We investigated the association between HO-1 promoter polymorphisms and nephropathy in type 2 diabetes. We sequenced the T(-413)A SNP and (GT)n repeat segments of the HO-1 gene promoter in 536 patients with type 2 diabetes. (GT)n alleles were divided into 2 groups: short (S, ≤25 GT repeats) and long (L, >25 GT repeats) alleles. The presence of albuminuria was used as a marker of diabetic nephropathy.Patients with the TT genotype in the T(-413)A SNP were significantly more susceptible to albuminuria development than those carrying the A allele, with an odds ratio of 1.577 (95% confidence interval, 1.088 - 2.285; P = 0.016). Subgroup analysis showed that patients carrying the TT genotype with long duration of diabetes (≥20 years), poor glycemic control, male gender and without hypertension had higher odds ratios for the development of albuminuria. In vitro, promoter activity of the T(-413)A SNP was higher with A allele than T allele. Regarding to the (GT)n repeats, the LL genotype showed a higher odds ratio for the development of albuminuria only in patients with hypertension when compared to the S allele.In conclusion, the T(-413)A SNP in the HO-1 promoter is significantly associated with albuminuria development in type 2 diabetes patients, especially with longer duration and poor glycemic control.ope

Spontaneous bacterial peritonitis in patients with hepatitis B virus-related liver cirrhosis: community-acquired versus nosocomial

PURPOSE: Spontaneous bacterial peritonitis (SBP) frequently develops in patients with liver cirrhosis; however, there is little data to suggest whether the acquisition site of infection influences the prognosis. This study compared the bacteriology, clinical characteristics and treatment outcomes of community-acquired SBP (CA-SBP) and nosocomial SBP (N-SBP). MATERIALS AND METHODS: The medical records of 130 patients with hepatitis B virus (HBV)-related liver cirrhosis, who had experienced a first episode of SBP between January 1999 and December 2008, were reviewed. RESULTS: The study population included 111 (85.4%) patients with CA-SBP and 19 (14.6%) patients with N-SBP. Baseline and microbiological characteristics as well as clinical course, including in-hospital mortality, did not differ between patients with CA-SBP and those with N-SBP (all p>0.05). The median survival time was 6.5 months, and 117 (90.0%) patients died during the follow-up period. Patients with CA-SBP and N-SBP survived for median periods of 6.6 and 6.2 months, respectively, without significant difference (p=0.569). Time to recurrence did not differ between patients with CA-SBP and N-SBP (4.7 vs. 3.6 months, p=0.925). CONCLUSION: The acquisition site of infection did not affect clinical outcomes for patients with HBV-related liver cirrhosis who had experienced their first episode of SBP. Third-generation cephalosporins may be effective in empirically treating these patients, regardless of the acquisition site of the infection.ope

Predicting Liver-Related Events Using Transient Elastography in Chronic Hepatitis C Patients with Sustained Virological Response.

BACKGROUND/AIMS: Few studies have investigated prognostic factors for the development of liver-related events (LREs) in patients with chronic hepatitis C (CHC) who achieve sustained virological response (SVR). METHODS: We analyzed 190 patients with CHC who achieved SVR after treatment with pegylated interferon (peg-IFN) plus ribavirin. LREs were defined as any complications related to cirrhosis, hepatocellular carcinoma (HCC), or liver-related mortality. RESULTS: The mean age was 54.1 years, and 84 of the patients (44.2%) were male. The mean liver stiffness (LS) value at SVR was 7.1±5.4 kPa. During the follow-up period (median, 43.0 months), LREs occurred in 10 patients (5.3%; HCC in eight patients, ascites in one patient, and liver-related mortality in one patient). By multivariate Cox regression analysis, age, α-fetoprotein level, and LS value were independent predictors for LRE development (all p<0.05). Patients with LS values ≥7.0 kPa had a greater risk (hazard ratio, 9.472; 95% confidence interval, 1.018 to 88.126; p=0.048) for LRE development compared to those with LS values <7.0 kPa. CONCLUSIONS: The LS value at SVR is useful for predicting LRE development in CHC patients who achieve SVR after treatment with peg-IFN plus ribavirin. Thus, LRE surveillance strategies might be optimized according to the LS values at SVR, even with complete viral eradication.ope