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A case of Alagille syndrome presenting with chronic cholestasis in an adult.

Jihye KIM ; Bumhee YANG ; Namyoung PAIK ; Yon Ho CHOE ; Yong Han PAIK

Clinical and Molecular Hepatology.2017;23(3):260-264. doi:10.3350/cmh.2016.0057

Alagille syndrome (AGS) is a complex multisystem disorder that involves mainly the liver, heart, eyes, face, and skeleton. The main associated clinical features are chronic cholestasis due to a paucity of intrahepatic bile ducts, congenital heart disease primarily affecting pulmonary arteries, vertebral abnormalities, ocular embryotoxon, and peculiar facies. The manifestations generally become evident at a pediatric age. AGS is caused by defects in the Notch signaling pathway due to mutations in JAG1 or NOTCH2. It is inherited in an autosomal dominant pattern with a high degree of penetrance, but variable expressivity results in a wide range of clinical features. Here we report on a 31-year-old male patient who presented with elevated serum alkaline phosphatase and gamma-glutamyl transpeptidase, and was diagnosed with AGS associated with the JAG1 mutation after a comprehensive workup.
Adult* ; Alagille Syndrome* ; Alkaline Phosphatase ; Bile Ducts, Intrahepatic ; Cholestasis* ; Facies ; gamma-Glutamyltransferase ; Heart ; Heart Defects, Congenital ; Humans ; Liver ; Male ; Penetrance ; Pulmonary Artery ; Skeleton

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Protein and vitamin B6 intake are associated with liver steatosis assessed by transient elastography, especially in obese individuals.

Yvelise FERRO ; Ilaria CARÈ ; Elisa MAZZA ; Francesco PROVENZANO ; Carmela COLICA ; Carlo TORTI ; Stefano ROMEO ; Arturo PUJIA ; Tiziana MONTALCINI

Clinical and Molecular Hepatology.2017;23(3):249-259. doi:10.3350/cmh.2017.0019

BACKGROUND/AIMS: Although the detrimental effects of several dietary components on the promotion of nonalcoholic fatty liver disease are well known, no studies have assessed the role of dietary vitamin B6. Moreover, studies on the associations between dietary components or body composition indices and liver steatosis assessed by transient elastography are rare. Our aim was to identify the nutritional factors and anthropometric parameters associated with liver steatosis. METHODS: In this cross-sectional study, we enrolled 168 individuals (35% obese) who underwent a liver steatosis assessment by Controlled Attenuation Parameter measurement and nutritional assessment. RESULTS: Tertiles of vitamin B6 intake were positively associated with hepatic steatosis (B=1.89, P=0.026, confidence interval [CI] 0.03-0.80) as well as with triglycerides, glucose, alanine aminotransferase (ALT), and body mass index . In obese individuals, after multivariable analysis, the Controlled Attenuation Parameter score was still associated with triglycerides, ALT, and total protein intake (B=0.56, P=0.01, CI 0.10-1.02). Participants in tertile I (low intake) had a lower Controlled Attenuation Parameter than those in tertile III (P=0.01). CONCLUSIONS: We found a positive association between hepatic steatosis or Controlled Attenuation Parameter score and vitamin B6/total protein intake, probably related to the high intake of meat. Vitamin B6 might have a pathogenic role related to the increase of hepatic steatosis.
Alanine Transaminase ; Body Composition ; Body Mass Index ; Cross-Sectional Studies ; Elasticity Imaging Techniques* ; Fatty Liver* ; Glucose ; Liver* ; Meat ; Non-alcoholic Fatty Liver Disease ; Nutrition Assessment ; Obesity ; Triglycerides ; Vitamin B 6* ; Vitamins*

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Pitfalls in surveillance for hepatocellular carcinoma: How successful is it in the real world?.

Linda L. WONG ; Ruel J REYES ; Sandi A KWEE ; Brenda Y HERNANDEZ ; Sumodh C KALATHIL ; Naoky C TSAI

Clinical and Molecular Hepatology.2017;23(3):239-248. doi:10.3350/cmh.2017.0008

BACKGROUND/AIMS: Surveillance for hepatocellular carcinoma (HCC) with ultrasound in high-risk populations is generally believed to improve opportunities for treatment. However, tumors are still missed due to various factors. This study explores success versus failure of HCC surveillance. METHODS: This is a retrospective study of 1,125 HCC cases. Categories considered for successful detection were largest tumor ≤3.0 cm, single tumors ≤3.0 cm and ≤2.0 cm, and adherence to Milan criteria. Examined factors were age <60 years, gender, rural residence, body-mass index (BMI), hepatitis infection, smoking, diabetes, hyperlipidemia, cirrhosis, ascites, and Model for End-Stage Liver Disease <10. RESULTS: HCC was found on surveillance in 257 patients with a mean tumor size of 3.17 cm; multiple tumors were seen in 28% of cases, bilateral tumors in 7.4%, and vascular invasion in 3.7%. Surveillance was successful in 61.5% of cases involving a largest tumor ≤3.0 cm, with BMI ≥35 negatively affecting detection (odds ratio [OR] 0.28, P=0.014) and cirrhosis positively affecting detection (OR 2.31, P=0.036). Ultrasound detected 19.1% of single tumors ≤2.0 cm with ascites improving the detection rate (OR 3.89, P=0.001). Finally, adherence to Milan criteria occurred in 75.1% of cases, revealing negative associations with diabetes (OR 0.48, P=0.044 and male gender (OR 0.49, P=0.08). CONCLUSIONS: Although surveillance is recommended for HCC, not all surveillance ultrasound are ideal. Tumor detection can depend on gender, BMI, diabetes, cirrhosis, and ascites and is achieved in 19.1–75% of cases depending on the definition of success. Closer follow-up or additional imaging might be necessary for some patient subgroups.
Ascites ; Carcinoma, Hepatocellular* ; Early Detection of Cancer ; Fibrosis ; Follow-Up Studies ; Hepatitis ; Humans ; Hyperlipidemias ; Liver Diseases ; Male ; Population Surveillance ; Retrospective Studies ; Smoke ; Smoking ; Ultrasonography

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Efficacy of tenofovir-based rescue therapy for chronic hepatitis B patients with resistance to lamivudine and entecavir.

Hee Jeong JEON ; Seok Won JUNG ; Neung Hwa PARK ; Yujin YANG ; Jin Hee NOH ; Jae Sung AHN ; Hyung Rae KIM ; Jae Ho LEE ; Jung Woo SHIN

Clinical and Molecular Hepatology.2017;23(3):230-238. doi:10.3350/cmh.2017.0003

BACKGROUND/AIMS: Tenofovir disoproxil fumarate (TDF) monotherapy for 48 weeks provided a virological response comparable to that of TDF and entecavir (ETV) combination therapy in patients infected with ETV-resistant hepatitis B virus (HBV). Little long-term data in routine clinical practice are available regarding the optimal treatment of patients with ETV-resistant HBV. METHODS: We investigated the long-term antiviral efficacy of combination therapy of TDF+lamivudine (LAM) or TDF+ETV compared to that of TDF monotherapy in 73 patients with resistance to both LAM and ETV. RESULTS: Patients were treated with TDF monotherapy (n=12), TDF+LAM (n=19), or TDF+ETV (n=42) for more than 6 months. The median duration of TDF-based rescue therapy was 37 months. Virologic response (VR) was found in 63 patients (86.3%). The rates of VR among the three groups (TDF monotherapy, TDF+LAM, and TDF+ETV) were not statistically different (log-rank P=0.200) at 12 months (59.3%, 78.9%, and 51.8%, respectively) or at 24 months (88.4%, 94.7%, and 84.2%). In addition, treatment efficacy of TDF-based combination or TDF monotherapy was not statistically different with ETV-resistant strains or exposure to other antiviral agents. In multivariate analysis, only lower baseline HBV DNA level was an independent predictor for VR (hazard ratio, 0.723; 95% confidence interval, 0.627-0.834; P<0.001). CONCLUSIONS: TDF monotherapy was as effective as combination therapy of TDF+LAM or TDF+ETV in maintaining long-term viral suppression in chronic hepatitis B patients with resistance to both LAM and ETV. HBV DNA level at the start of TDF rescue therapy was the only independent predictor of subsequent VR.
Antiviral Agents ; DNA ; Hepatitis B virus ; Hepatitis B, Chronic* ; Hepatitis, Chronic* ; Humans ; Lamivudine* ; Multivariate Analysis ; Tenofovir ; Treatment Outcome

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Influence of ultrasound contrast agents on spectral Doppler analysis in recipients of liver transplantation.

Young Seo CHO ; Kyoung Won KIM ; Hye Young JANG ; Bo Hyun KIM ; Jeongjin LEE ; Gi Won SONG ; Sung Gyu LEE ; Dagvasumberel MUNKHBAATAR

Clinical and Molecular Hepatology.2017;23(3):224-229. doi:10.3350/cmh.2016.0064

BACKGROUND/AIMS: Clinical validation is required to determine whether Doppler measurements are comparable before and after administering ultrasound contrast agent (USCA). The purpose of this study is to explore whether the use of USCA affects spectral Doppler analysis in recipients of liver transplantation (LT). METHODS: For this study, 36 patients were examined using Doppler ultrasonography (US) along with a contrast-enhanced US for surveillance of vascular complications after LT. The following spectral Doppler US parameters were measured before and after administration of USCA: peak systolic velocity, end-diastolic velocity, resistive index, and systolic acceleration time of the graft hepatic artery; peak flow velocity of the graft portal vein; and peak flow velocity and venous pulsatility index of the graft hepatic vein. RESULTS: The mean peak systolic and end-diastolic velocities of the hepatic artery and the peak flow velocity of the portal and hepatic veins were increased after intravenously administration of the USCA, ranging from 10% to 13%. However, the changes were not statistically significant (P=0.097, 0.103, 0.128, and 0.190, respectively). There were no significant differences in other measured parameters, including the resistive index (P=0.205) and systolic acceleration time (P=0.489) of the hepatic artery and venous pulsatility index (P=0.494) of the hepatic vein. CONCLUSIONS: The measured velocities of graft hepatic vessels tended to increase after administration of USCA, but without statistical significance. The comparison of serial Doppler parameters with or without injection of USCA is valid during Doppler surveillance in recipients of LT.
Acceleration ; Contrast Media* ; Doppler Effect ; Hepatic Artery ; Hepatic Veins ; Humans ; Liver Transplantation* ; Liver* ; Microbubbles ; Portal Vein ; Transplants ; Ultrasonography* ; Ultrasonography, Doppler

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Surveillance of hepatocellular carcinoma: is only ultrasound enough?.

Woo Kyoung JEONG

Clinical and Molecular Hepatology.2017;23(3):222-223. doi:10.3350/cmh.2017.0046

No abstract available.
Carcinoma, Hepatocellular* ; Ultrasonography*

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Is tenofovir monotherapy a sufficient defense line against multi-drug resistant hepatitis B virus?.

Yun Bin LEE ; Jeong Hoon LEE

Clinical and Molecular Hepatology.2017;23(3):219-221. doi:10.3350/cmh.2017.0045

No abstract available.
Drug Resistance, Multiple ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis B, Chronic ; Hepatitis* ; Tenofovir*

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Current status of and strategies for hepatitis C control in South Korea.

Beom Kyung KIM ; Eun Sun JANG ; Jeong Han KIM ; Soo Young PARK ; Song Vogue AHN ; Hyung Joon KIM ; Do Young KIM

Clinical and Molecular Hepatology.2017;23(3):212-218. doi:10.3350/cmh.2017.0105

Chronic hepatitis C (CHC) is caused by hepatitis C virus (HCV) infection. HCV infection causes acute hepatitis, and the majority of those infected progress to chronic hepatitis, and some of them develop cirrhosis and hepatocellular carcinoma. Transmission of HCV is parenteral, and the major transmission routes include drug abuse, insecure injections or medical procedures, contaminated syringes or needles, sexual contact with an HCV-infected person, vertical infection of newborns by infected mothers, the transfusion of blood or blood products contaminated with viruses, and organ transplants. As no vaccine against HCV is available, HCV management involves blocking routes of transmission transmission, screening for HCV infection, and protecting liver disease progression by treatment. Highly potent oral direct antiviral agents are now available. Therefore, early detection through nation-wide screening program and appropriate treatment should be implemented to improve the quality of life of patients with HCV. Furthermore, for the effective HCV control in South Korea, The organization of an ‘integrated national viral hepatitis control system’ is desirable.
Antiviral Agents ; Carcinoma, Hepatocellular ; Fibrosis ; Hepacivirus ; Hepatitis C* ; Hepatitis C, Chronic ; Hepatitis* ; Hepatitis, Chronic ; Humans ; Infant, Newborn ; Korea* ; Liver Diseases ; Mass Screening ; Mothers ; Needles ; Quality of Life ; Substance-Related Disorders ; Syringes ; Transplants

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Current status and strategies for hepatitis B control in Korea.

Eun Ju CHO ; Sung Eun KIM ; Ki Tae SUK ; Jihyun AN ; Soung Won JEONG ; Woo Jin CHUNG ; Yoon Jun KIM

Clinical and Molecular Hepatology.2017;23(3):205-211. doi:10.3350/cmh.2017.0104

Hepatitis B virus (HBV) infection is the most common cause of chronic liver diseases in Korea. After the introduction of the universal HBV vaccination program, the prevalence of hepatitis B surface antigen was markedly reduced, and Korea is now classified as an area of intermediate endemicity for HBV. However, there are still hurdles for elimination of hepatitis B, such as immunoprophylaxis failure against vertical transmission, occurrence of acute hepatitis B among peoples who did not have vaccination at younger age, and rapid increase of immigrant populations from HBV endemic areas. To achieve the World Health Organization goal of viral hepatitis elimination by 2030 in Korea, we suggest comprehensive policies for more effective control of hepatitis B as following: i) insurance coverage for antiviral prophylaxis in mothers with high viremia, ii) screening for hepatitis B seromarkers and catch-up HBV vaccinations of susceptible persons with hepatitis B, iii) establishment of an independent ‘viral hepatitis sector’ in Centers for Disease Control & Prevention to organize and execute comprehensive strategy for management of viral hepatitis, iv) encourage of management of HBV infection in immigrant populations, v) national campaign to promote awareness of hepatitis B.
Centers for Disease Control and Prevention (U.S.) ; Emigrants and Immigrants ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B* ; Hepatitis* ; Humans ; Insurance Coverage ; Korea* ; Liver Diseases ; Mass Screening ; Mothers ; Prevalence ; Vaccination ; Viremia ; World Health Organization

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Current status and strategies for the control of viral hepatitis A in Korea.

Eileen L YOON ; Dong Hyun SINN ; Hyun Woong LEE ; Ji Hoon KIM

Clinical and Molecular Hepatology.2017;23(3):196-204. doi:10.3350/cmh.2017.0034

Hepatitis A virus is one of the most frequent causes of foodborne infection, which is closely associated with sanitary conditions and hygienic practices. The clinical spectrum of acute hepatitis A is wide, ranging from mild case without any noticeable symptoms to severe case with acute liver failure leading to mortality. The severity and outcome are highly correlated with age at infection. In developing countries, most people are infected in early childhood without significant symptom. Ironically, in area where sanitary condition has improved rapidly, adults who do not have immunity for viral hepatitis A (VH-A) in early childhood is accumulating. Adults without immunity are exposed to risks of symptomatic disease and large outbreaks in society. In Korea, where hygiene has improved rapidly, acute hepatitis A is a significant health burden that needs to be managed with nationwide health policy. The incidence of symptomatic VH-A has increased since 2000 and peaked in 2009. Korea has designated hepatitis A as a group 1 nationally notifiable infectious disease in 2001. Since 2001, mandatory surveillance system has been established to detect every single case of acute hepatitis A. Universal, nationwide vaccination program for newborns was introduced in 2015. In this review, we will present the current epidemiologic status of viral hepatitis A, and evaluate the effectiveness of the current nationwide strategies for the control of viral hepatitis A in Korea. Furthermore, we presented some action proposals that can help eliminate viral hepatitis A, which is a significant health burden in Korea.
Adult ; Communicable Diseases ; Developing Countries ; Disease Outbreaks ; Health Policy ; Hepatitis A virus ; Hepatitis A* ; Hepatitis* ; Humans ; Hygiene ; Incidence ; Infant, Newborn ; Iron ; Korea* ; Liver Failure, Acute ; Mortality ; Vaccination

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