OBJECTIVETo investigate the value of controlled attenuation parameter (CAP) in the diagnosis of fatty liver using FibroScan in patients with chronic liver disease (CLD).

METHODSA prospective cohort study was performed for the patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC), and non-alcoholic fatty liver disease (NAFLD) who underwent liver pathological examination followed by CAP measurement within 1 week in The Second People's Hospital of Tianjin from February 2013 to May 2014. According to related guidelines, hepatocyte steatosis was classified as S0: <5%, S1: 5%-33%, S2: 34%-66%, or S3: ≥67%. The receiver operating characteristic (ROC) curves were plotted with positive results as the diagnostic criteria, and the optimal cut-off values were determined at the maximum Youden index. Single linear regression and multiple stepwise regression were applied to analyze the influencing factors for CAP.

RESULTSA total of 427 patients were enrolled, consisting of 19 patients (4.4%) with NAFLD, 383 (89.7%) with CHB, and 25 (5.9%) with CHC. The optimal cut-off values for CAP in the diagnosis of steatosis ≥5%, ≥34%, and ≥67% were 230 dB/m, 252 dB/m, and 283 dB/m, respectively, and the areas under the ROC curve were 0.803, 0.942, and 0.938, respectively (Z = 14.194, 28.385, and 16.486, respectively, all P < 0.01). CAP differentiated S0 from S1, S1 from S2, S0 from S2, S0 from S3, and S1 from S3 (Z = 10.109, 10.224, 47.81, 29.917, and 10.999, all P < 0.01), but was not able to differentiate S2 from S3 (Z = 0.656, P = 0.5116). The single linear regression and multiple stepwise regression analyses showed that only body mass index (BMI; B = 4.001, P < 0.01) and hepatic steatosis (B = 33.015, P = 0.000) were correlated with CAP. The coincidence rates between CAP and liver pathological diagnosis were 77.4%, 81.0%, and 96.2% for S0, S3, and ≥S2, respectively.

CONCLUSIONCAP has a good value in the diagnosis of fatty liver in CLD patients, and can well differentiate between all stages of fatty liver except S2 and S3. CAP is influenced by BMI, but is not found to be associated with liver fibrosis, inflammation, liver stiffness measurement, and etiology.

Area Under Curve ; Biopsy ; Body Mass Index ; Cell Differentiation ; Elasticity Imaging Techniques ; Hepatitis B, Chronic ; complications ; Hepatitis C, Chronic ; complications ; Humans ; Inflammation ; complications ; Linear Models ; Liver Cirrhosis ; complications ; Multivariate Analysis ; Non-alcoholic Fatty Liver Disease ; complications ; diagnosis ; Prospective Studies ; ROC Curve

Hepatocellular carcinoma (HCC) can be diagnosed based on characteristic findings of arterial-phase enhancement and portal/delayed "washout" in cirrhotic patients. Several countries and major academic societies have proposed varying specific diagnostic criteria for HCC, largely reflecting the variable HCC prevalence in different regions and ethnic groups, as well as different practice patterns. In 2014, a new version of Korean practice guidelines for management of HCC was released by the Korean Liver Cancer Study Group (KLCSG) and the National Cancer Center (NCC). According to the KLCSG-NCC Korea practice guidelines, if the typical hallmark of HCC (i.e., hypervascularity in the arterial phase with washout in the portal or 3 min-delayed phases) is identified in a nodule > or = 1 cm in diameter on either dynamic CT, dynamic MRI, or MRI using hepatocyte-specific contrast agent in high-risk groups, a diagnosis of HCC is established. In addition, the KLCSG-NCC Korea practice guidelines provide criteria to diagnose HCC for subcentimeter hepatic nodules according to imaging findings and tumor marker, which has not been addressed in other guidelines such as Association for the Study of Liver Diseases and European Association for the Study of the Liver. In this review, we briefly review the new HCC diagnostic criteria endorsed by the 2014 KLCSG-NCC Korea practice guidelines, in comparison with other recent guidelines; we furthermore address several remaining issues in noninvasive diagnosis of HCC, including prerequisite of sonographic demonstration of nodules, discrepancy between transitional phase and delayed phase, and implementation of ancillary features for HCC diagnosis.
Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular/*diagnosis/pathology ; Contrast Media ; Female ; Hepatitis B, Chronic/complications ; Hepatitis C, Chronic/complications ; Humans ; Liver/*pathology ; Liver Neoplasms/*diagnosis/pathology ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; Practice Guidelines as Topic ; Republic of Korea ; Young Adult

BACKGROUND/AIMS: The previous standard treatment for chronic hepatitis C (CHC) patients, comprising a combination of pegylated interferon (IFN) and ribavirin, was associated with suboptimal efficacy and severe adverse reactions. A new era of direct-acting antivirals is now dawning in Korea. Early experience of applying sofosbuvir-based therapy to CHC patients in Korea is reported herein. METHODS: Data on efficacy and safety were collected for CHC patients treated with a combination of sofosbuvir plus ribavirin or sofosbuvir/ledipasvir with or without ribavirin. RESULTS: This retrospective study included 25 consecutive patients who received sofosbuvir-based therapy (19 with genotype 1b and 6 with genotype 2) at Seoul National University Hospital from May 2014 to April 2015. A virologic response was achieved at week 4 by 85.7% and 80% of the patients with genotypes 1b and 2, respectively. The HCV-RNA level decreased more slowly in IFN-experienced than in treatment-naive patients with genotype 1b. However, the sustained virologic response at week 12 (SVR12) rate did not differ among these patients, and was as high as 100%. The presence of cirrhosis significantly increased the risk of a virologic response failure at week 4 (OR, 11.0; P=0.011) among patients with HCV genotype 1b. Only five patients (20%) experienced minor adverse events, including grade 1 fatigue and headache. The hemoglobin level decreased slightly after sofosbuvir-based therapy, but there was no case of premature discontinuation of this therapy. CONCLUSIONS: In a real clinical practice, sofosbuvir-based therapy for CHC patients in Korea achieved optimal antiviral efficacy with insignificant adverse events. Long-term follow-up data are warranted to ensure the sustained antiviral efficacy and long-term safety of sofosbuvir-based IFN-free therapy.
Adult ; Aged ; Aged, 80 and over ; Antiviral Agents/adverse effects/*therapeutic use ; Drug Therapy, Combination ; Fatigue/etiology ; Female ; Genotype ; Headache/etiology ; Hemoglobins/analysis ; Hepacivirus/genetics ; Hepatitis C, Chronic/complications/*drug therapy/virology ; Humans ; Liver Cirrhosis/complications/diagnosis ; Male ; Middle Aged ; RNA, Viral/blood ; Republic of Korea ; Retrospective Studies ; Ribavirin/therapeutic use ; Sofosbuvir/adverse effects/*therapeutic use ; Treatment Outcome

BACKGROUNDChronic hepatitis C virus (HCV) infection can affect multiple organ systems and cause a variety of extrahepatic manifestations (EMs). We sought to assess the constituent ratio of EMs in Chinese patients with chronic HCV infection and identify the clinical and biological factors associated with EM.

METHODSThe medical records of 297 patients with chronic HCV infection were analyzed and demographic and epidemiological information was collected. The diagnosis of chronic HCV infection was based on positive anti-HCV combined with a positive HCV-RNA or at least two times of elevated aminotransferases attributable to HCV infection. Patients with HBV and/or HIV coinfection, autoimmune hepatitis, and history of alcohol abuse were excluded.

RESULTSSixty-two percent (184/297) of the patients had at least one EM, including fatigue (29.4%), type 2 diabetes mellitus (28.2%), renal involvement (12.5%), lymphadenopathy (9.6%), fever (9.4%), thyroid dysfunction (8.1%), and arthralgia (7.4%). Neuropathy, sicca syndrome, B-cell lymphoma, Raynaud's phenomenon, and lichen planus were rare. The mean age of patients with EM was older compared with those without EM.

CONCLUSIONSEMs were common in Chinese patients with chronic HCV infection, particularly fatigue, type 2 diabetes, renal impairment, lymphadenophy, fever, and thyroid dysfunction. Older age was associated with EMs.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; China ; Cryoglobulinemia ; diagnosis ; etiology ; Diabetes Mellitus, Type 2 ; diagnosis ; etiology ; Fatigue ; diagnosis ; etiology ; Female ; Hepatitis C, Chronic ; complications ; physiopathology ; Humans ; Lymphatic Diseases ; diagnosis ; etiology ; Male ; Middle Aged ; Thrombocytopenia ; diagnosis ; etiology ; Young Adult

Cryptococcus neoformans, an encapsulated fungus, is an important opportunistic pathogen that can cause meningitis in immunocompromised patients. Since patients with cryptococcemia have high mortality, it is essential to make an early diagnosis and promptly initiate antifungal therapy. However, it is often very difficult to differentiate between cryptococcal meningitis and hepatic encephalopathy in patients with liver cirrhosis, and there is delay in making the diagnosis. Therefore, these patients have a particularly grave prognosis and consequently many patients die before culture results become available. In one study, starting antifungal therapy within 48 hours of the blood culture was associated with improved survival, but patients with liver cirrhosis were significantly less likely to receive antifungal therapy within 48 hours compared to those without liver cirrhosis. Recently, the authors experience a case of a 68-year-old woman with liver cirrhosis who presented with fever and a drowsy mental status. She had a previous history of having been admitted for infection-associated hepatic encephlopathy. Cryptococcal meningitis and cryptococcemia were diagnosed by spinal puncture and culture of cerebrospinal fluid. In spite of adequate treatment, the patient developed multi-system organ failure and eventually expired. Herein, we report a case of cryptococcal meningitis mimicking hepatic encephalopathy in a patient with liver cirrhosis.
Aged, 80 and over ; Brain/radiography ; Cryptococcus/isolation & purification ; Female ; Hepatic Encephalopathy/complications/*diagnosis ; Hepatitis C, Chronic/complications/pathology ; Humans ; Liver Cirrhosis/etiology/pathology ; Meningitis, Cryptococcal/complications/*diagnosis/microbiology ; Tomography, X-Ray Computed

Hepatitis C virus (HCV) is one of the main viral causes of hepatocellular carcinoma (HCC) and is associated with lymphoproliferative disorder such as non-Hodgkin's lymphoma (NHL). However, there are only few case reports on concomitantly induced NHL and HCC by HCV. Herein, we report a case of synchronous NHL and HCC in a patient with chronic hepatitis C which was unexpectedly diagnosed during liver transplantation surgery. This case suggests that although intrahepatic lymph node enlargements are often considered as reactive or metastatic lymphadenopathy in chronic hepatitis C patients with HCC, NHL should also be considered as a differential diagnosis.
Antineoplastic Agents/therapeutic use ; Carcinoma, Hepatocellular/complications/*diagnosis/radiotherapy ; Drug Therapy, Combination ; Embolization, Therapeutic ; Fluorodeoxyglucose F18 ; Gadolinium DTPA ; Genotype ; Hepatitis B virus/genetics ; Hepatitis C, Chronic/complications/*diagnosis/*virology ; Humans ; Liver Neoplasms/complications/*diagnosis/radiotherapy ; Lymph Nodes/pathology ; Lymphoma, Non-Hodgkin/complications/*diagnosis/drug therapy ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Positron-Emission Tomography ; Tomography, X-Ray Computed

BACKGROUND/AIMS: Liver stiffness measurement (LSM) has been proposed as a non-invasive method for estimating the severity of fibrosis and the complications of cirrhosis. Measurement of the hepatic venous pressure gradient (HVPG) is the gold standard for assessing the presence of portal hypertension, but its invasiveness limits its clinical application. In this study we evaluated the relationship between LSM and HVPG, and the predictive value of LSM for clinically significant portal hypertension (CSPH) and severe portal hypertension in cirrhosis. METHODS: LSM was performed with transient elastography in 59 consecutive cirrhotic patients who underwent hemodynamic HVPG investigations. CSPH and severe portal hypertension were defined as HVPG > or =10 and > or =12 mmHg, respectively. Linear regression analysis was performed to evaluate the relationship between LSM and HVPG. Diagnostic values were analyzed based on receiver operating characteristic (ROC) curves. RESULTS: A strong positive correlation between LSM and HVPG was observed in the overall population (r2=0.496, P<0.0001). The area under the ROC curve (AUROC) for the prediction of CSPH (HVPG > or =10 mmHg) was 0.851, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for an LSM cutoff value of 21.95 kPa were 82.5%, 73.7%, 86.8%, and 66.7%, respectively. The AUROC at prediction of severe portal hypertension (HVPG > or =12 mmHg) was 0.877, and the sensitivity, specificity, PPV, and NPV at LSM cutoff value of 24.25 kPa were 82.9%, 70.8%, 80.6%, and 73.9%, respectively. CONCLUSIONS: LSM exhibited a significant correlation with HVPG in patients with cirrhosis. LSM could be a non-invasive method for predicting CSPH and severe portal hypertension in Korean patients with liver cirrhosis.
Adult ; Aged ; Alcohol-Related Disorders/complications ; Area Under Curve ; *Elasticity Imaging Techniques ; Female ; Hepatitis B/complications ; Hepatitis C/complications ; Humans ; Hypertension, Portal/*complications/*diagnosis ; Linear Models ; Liver Cirrhosis/*complications/*diagnosis/pathology ; Male ; Middle Aged ; ROC Curve ; Republic of Korea ; Sensitivity and Specificity

Occult HBV infection is defined as the presence of HBV DNA in the liver (with or without detectable or undetectable HBV DNA in the serum) of individuals testing negative for HBsAg. Studies on occult HBV infection in hepatitis C patients have reported highly variable prevalence, because the prevalence of occult HBV infection varies depending on the hepatitis B risk factors and methodological approaches. The most reliable diagnostic approach for detecting occult HBV detection is through examination of liver DNA extracts. HCV has been suspected to strongly suppress HBV replication up to the point where it may be directly responsible for occult HBV infection development. However, more data are needed to arrive at a definitive conclusion regarding the role of HCV in inducing occult HBV infection. Occult HBV infection in chronic hepatitis C patients is a complex biological entity with possible relevant clinical implications. Influence of occult HBV infection on the clinical outcomes of chronic hepatitis C may be considered negative. However, recent studies have shown that occult HBV infection could be associated with the development of hepatocellular carcinoma and contribute to the worsening of the course of chronic liver disease over time in chronic hepatitis C patients. Nevertheless, the possible role of occult HBV infection in chronic hepatitis C is still unresolved and no firm conclusion has been made up until now. It still remains unclear how occult HBV infection affects the treatment of chronic hepatitis C. Therefore, in order to resolve current controversies and understand the pathogenic role and clinical impacts of occult HBV infection in chronic hepatitis C patients, well-designed clinical studies are needed.
Carcinoma, Hepatocellular/complications ; DNA, Viral/analysis ; Hepacivirus/genetics ; Hepatitis B/*complications/*diagnosis/drug therapy ; Hepatitis B virus/genetics ; Hepatitis C, Chronic/*complications/*diagnosis/drug therapy ; Humans ; Interferon-alpha/therapeutic use ; Liver/virology ; Liver Neoplasms/complications

Several studies have reported that ABO blood group, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection contribute to the development of pancreatic cancer. The aim of this study was to evaluate the association between these factors and pancreatic cancer in the Korean population. We retrospectively recruited 753 patients with pancreatic cancer and 3,012 healthy controls, matched 4 to 1 with cancer patients for age and sex, between 2001 and 2011, at the National Cancer Center, Korea. A multivariate logistic regression analysis was employed to estimate adjusted odds ratios (AORs). The AOR for pancreatic cancer in subjects with non-O blood types (A, AB, and B), compared to blood type O, was 1.29 (95% CI, 1.05-1.58; P = 0.01). Seropositivity for hepatitis B virus surface antigen was not significantly related to pancreatic cancer, either in univariate (odds ratio 1.03; 95% CI, 0.69-1.53; P = 0.91) or multivariate analysis (AOR, 1.02; 95% CI, 0.67-1.56; P = 0.93). The AOR for pancreatic cancer in subjects displaying seropositivity for anti-HCV was 2.30 (95% CI, 1.30-4.08; P < 0.01). Our results suggest that the non-O blood types and anti-HCV seropositivity, but not HBV infection, may increase the risk of developing pancreatic cancer in Korea, where HBV is endemic.
ABO Blood-Group System ; Aged ; Case-Control Studies ; Female ; Hepatitis B/complications/diagnosis ; Hepatitis B Surface Antigens/blood ; Hepatitis C/*complications/diagnosis ; Hepatitis C Antibodies/blood ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Pancreatic Neoplasms/diagnosis/*etiology ; Republic of Korea ; Retrospective Studies ; Risk Factors

Variceal bleeding and hepatorenal syndrome (HRS) are serious and life-threatening complications of advanced liver disease. Terlipressin is widely used to manage both acute variceal bleeding and HRS due to its potency and long duration of action. The most severe (though rare) adverse event is ischemia. The present report describes the case of a patient with gangrene and osteomyelitis secondary to terlipressin therapy. A 71-year-old male with alcoholic liver cirrhosis (Child-Pugh B) and chronic hepatitis C was admitted due to a drowsy mental status. The patient had several experiences of orthopedic surgery. His creatinine level had gradually elevated to 4.02 mg/dL, and his urine output decreased to 500 mL/24 hr. The patient was diagnosed as having grade III hepatic encephalopathy (HE) and type II HRS. Terlipressin and albumin were administered intravenously to treat the HRS over 11 days. Although he recovered from the HE and HRS, the patient developed peripheral gangrene and osteomyelitis in both feet. His right toes were cured with the aid of rescue therapy, but his left three toes had to be amputated. Peripheral gangrene and osteomyelitis secondary to terlipressin therapy occur only rarely, and there is no specific rescue therapy for these conditions. Thus, attention should be paid to the possibility of ischemia of the skin and bone during or after terlipressin therapy.
Aged ; Creatinine/blood ; Foot/pathology ; Gangrene/*etiology ; Hepatitis C, Chronic/complications ; Humans ; Liver Cirrhosis/complications/diagnosis ; Liver Diseases/*diagnosis/drug therapy ; Lypressin/adverse effects/*analogs & derivatives/therapeutic use ; Male ; Osteomyelitis/*etiology ; Severity of Illness Index ; Toe Phalanges/radiography ; Vasoconstrictor Agents/*adverse effects/therapeutic use