Hyunwoo Oh

Non-alcoholic fatty liver diseases: update on the challenge of diagnosis and treatment

The prevalence of non-alcoholic fatty liver disease (NAFLD) is estimated to be 25-30% of the population, and is the most common cause of elevated liver enzymes in Korea. NAFLD is a “hot potato” for pharmaceutical companies. Many clinical trials are underway to develop a first-in-class drug to treat NAFLD. However, there are several challenging issues regarding the diagnosis of NAFLD. Currently, liver biopsy is the gold standard method for the diagnosis of NAFLD and steatohepatitis. Ideally, globally recognized standards for histological diagnosis and methods to optimize observer agreement on biopsy interpretation should be developed. Liver biopsy is the best method rather than a perfect one. Recently, multi-parametric magnetic resonance imagery can estimate the amount of intrahepatic fat successfully and is widely used in clinical trials. But no diagnostic method can discriminate between steatohepatitis and simple steatosis. The other unresolved issue in regard to NAFLD is the absence of satisfactory treatment options. Vitamin E and obeticholic acid have shown protective effects in randomized controlled trials, but this drug has not been approved for use in Korea. This study will provide a description of diagnostic methods and treatments that are currently recommended for NAFLD.

Low Salt Diet and Insulin Resistance.

It is well known that high sodium intake is closely associated with the risk of cardiovascular disease, but the effect of low sodium intake on insulin resistance is not clear. In this article, we summarize findings from previous studies focusing on the association between low sodium intake and insulin resistance. While many investigations on this topic have been conducted actively, their major findings are inconsistent, partly due to different study designs. Thus, additional randomized controlled trials with an adequate study period and reasonable levels of low sodium intake are needed.

Ezetimibe decreased nonalcoholic fatty liver disease activity score but not hepatic steatosis

Background/Aims A number of clinical trials reported varying effects of cholesterol lowering agents in nonalcoholic fatty liver disease (NAFLD) patients. We, therefore, assessed the changes in hepatic steatosis and NAFLD activity score (NAS) after treatment with cholesterol lowering agents in NAFLD patients by metaanalysis. Methods The Cochrane Library, the MEDLINE, and the Embase databases were searched until May 2015, without any language restrictions, for randomized controlled trials (RCTs) and nonrandomized studies (NRSs). Additional references were obtained from review of bibliography of relevant articles. The quality of evidence was assessed using the grading of recommendations assessment, development and evaluation guidelines. Results Three RCTs (n = 98) and two NRSs (n = 101) met our study inclusion criteria (adult, NAFLD, liver biopsy). Liver biopsy was performed in all five studies, but only the three studies reported NAS. Ezetimibe significantly decreased NAS (standardized mean difference [SMD], –0.30; 95% confidence interval [CI], –0.57 to –0.03) but not hepatic steatosis in RCT (SMD, –0.1; 95% CI, –0.53 to 0.32), while the effect was significant for both NAS and intrahepatic content in NRSs (SMD, –3.0; 95% CI, –6.9 to 0.91). Conclusions Ezetimibe decreased NAS without improving hepatic steatosis.

The modified step-wise deflation method in blood pressure measurement

In non-invasive blood pressure (NIBP) measurement, most of the automatic devices use oscillometric method. There are two types of deflation in oscillometric method. One is the linear deflation and the other is the stepwise deflation method. In this study, we suggest the modified step deflation to reduce the measurement time while keeping the advantage of step deflation over linear deflation. With the control of the valve and real time signal processing, we implemented the blood pressure measurement system and new algorithm. We measure the amplitude of each systolic pulsation. For the validation of our suggested method, human observer assessed SBP / DBP according to EHS (European Hypertension Society) guideline. The mean differences between the suggested method and traditional auscultation method were 1.95 mmHg for SBP and -0.55 mmHg for DBP.

Long term outcome of antiviral therapy in patients with hepatitis B associated decompensated cirrhosis

AIM To investigate survival rate and incidence of hepatocellular carcinoma (HCC) in patients with decompensated cirrhosis in the antiviral era. METHODS We used the Korean Health Insurance Review and Assessment. Korea’s health insurance system is a public single-payer system. The study population consisted of 286871 patients who were prescribed hepatitis B antiviral therapy for the first time between 2007 and 2014 in accordance with the insurance guidelines. Overall, 48365 antiviral treatment-naïve patients treated between 2008 and 2009 were included, and each had a follow-up period ≥ 5 years. Data were analyzed for the 1st decompensated chronic hepatitis B (CHB) and treatment-naïve patients (n = 7166). RESULTS The mean patient age was 43.5 years. The annual mortality rates were 2.4%-19.1%, and 5-year cumulative mortality rate was 32.6% in 1st decompensated CHB treatment-naïve subjects. But the annual mortality rates sharply decreased to 3.4% (2.4%-4.9%, 2-5 year) after one year of antiviral treatment. Incidence of HCC at first year was 14.3%, the annual incidence of HCC decreased to 2.5% (1.8%-3.7%, 2-5 year) after one year. 5-year cumulative incidence of HCC was 24.1%. Recurrence rate of decompensated event was 46.9% at first year, but the annual incidence of second decompensation events in decompensated CHB treatment-naïve patients was 3.4% (2.1%-5.4%, 2-5 year) after one year antiviral treatment. 5-year cumulative recurrence rate of decompensated events was 60.6%. Meanwhile, 5-year cumulative mortality rate was 3.1%, and 5-year cumulative incidence of HCC was 11.5% in compensated CHB treatment-naïve patients. CONCLUSION Long term outcome of decompensated cirrhosis treated with antiviral agent improved much, and incidence of hepatocellular carcinoma and mortality sharply decreased after one year treatment.

Can We Trust Safety of Tenofovir Disoproxil in Patients with Decompensated Cirrhosis

Recently, Park et al., reported renal safety of tenofovir (TDF) in decompensated cirrhosis patients. Currently, most guidelines recommend the use of nucleos(t)ide analogues (NAs) for chronic hepatitis B (CHB) infection as a treatment of choice. Among the treatments, TDF and entecavir (ETV) are the two proven effective drugs for CHB patients. However, all NAs have potential risk for mitochondrial dysfunction, and TDF is particularly associated with proximal renal tubule damage. There are several reports regarding risk of TDF associated renal toxicity and osteoporosis. Although several studies emphasized the possibility that TDF might impair renal function and bone density; it is not clear whether this decline in renal function and bone density has clinical meaning. Therefore, we reviewed several studies on the renal safety of TDF and ETV. In the current issue, Park et al. conducted a single center retrospective cohort study of CHB patients with compensated and decompensated cirrhosis. At 96 weeks of observation, changes in estimated glomerular fraction rate (eGFR) and serum creatinine in TDF users were not statistically different with that of ETV users. There was no significant difference in number of patients showing more than 0.2 mg/dL increase in serum creatinine or 20% decrease in eGFR at the end points of the study. Multivariate analysis showed that baseline eGFR, diabetes, and diuretics use was associated with eGFR reduction of more than 20%, and the use of antiviral agents was not an independent risk factor for renal insufficiency incidence. It is still debatable whether TDF compared to ETV could decrease eGFR, which is both clinically and statistically significant. Lok et al., 11 studies meta-analysis showed no significant difference in renal safety profiles of TDF and ETV. However, Han et al., recently reviewed 12 studies, and showed that the incidence of creatinine increase and eGFR decrease was higher in TDF group compare to ETV group (relative risk, 1.601; 95% confidence interval, 1.035 to 2.478; p=0.0034; I=0.0%). Recent European Association for Study of the Liver (EASL) guidelines recommend the use of ETV rather than TDF in patients who are over 60 years, with bone disease or with decreased renal function (eGFR <60 mL/min, albuminuria, on hemodialysis). Park et al.’s paper is very interesting in several respects. First, all the study participants were cirrhotic. The studies focusing only on cirrhotic patients are rare. Although, about 12 studies comparing NAs safety have been published; however, most studies focused on hepatitis naïve patients, and the study sample did not had cirrhotic patients. Moreover, most studies did not even mention the exact proportion of cirrhosis patients, and sometimes decompensated cirrhosis patients were also excluded. Second, Park et al. provided detail information on changes of creatinine/eGFR over 2 years. Most studies simply suggested the prevalence of acute kidney injury (AKI) using various AKI criteria during different observation periods. However, the precise serum creatinine and eGFR changes were not mentioned. According to Han et al., systematic review, only two of 12 articles (including randomized controlled trial, cohort) mentioned quantitative numerical values regarding renal safety. In this paper, multivariate analysis showed that diuretics use, diabetes, and low eGFR are the risk factors for renal dysfunction which is not different from previous studies. Shin et al. analyzed 4,178 CHB patients and found that age, hypertension, diabetes, liver or kidney transplantation, underlying chronic kidney disease (CKD), and diuretics were the risk factors for renal insufficiency during NAs use. Importantly, the prevalence of diabetes and diuretics prescription also increases in decompensated cirrhosis. Al-