Cosmas Rinaldi A. Lesmana

Asia–Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update

There is great geographical variation in the distribution of hepatocellular carcinoma (HCC), with the majority of all cases worldwide found in the Asia–Pacific region, where HCC is one of the leading public health problems. Since the “Toward Revision of the Asian Pacific Association for the Study of the Liver (APASL) HCC Guidelines” meeting held at the 25th annual conference of the APASL in Tokyo, the newest guidelines for the treatment of HCC published by the APASL has been discussed. This latest guidelines recommend evidence-based management of HCC and are considered suitable for universal use in the Asia–Pacific region, which has a diversity of medical environments.

APASL consensus statements and recommendation on treatment of hepatitis C

The Asian-Pacific Association for the Study of the Liver (APASL) convened an international working party on the “APASL consensus statements and recommendation on management of hepatitis C” in March, 2015, in order to revise “APASL consensus statements and management algorithms for hepatitis C virus infection (Hepatol Int 6:409–435, 2012)”. The working party consisted of expert hepatologists from the Asian-Pacific region gathered at Istanbul Congress Center, Istanbul, Turkey on 13 March 2015. New data were presented, discussed and debated to draft a revision. Participants of the consensus meeting assessed the quality of cited studies. Finalized recommendations on treatment of hepatitis C are presented in this review.

Non-invasive assessment of portal hypertension and liver fibrosis using contrast-enhanced ultrasonography.

Portal hypertension and hepatic fibrosis are key pathophysiologies with major manifestations in cirrhosis. Although the degree of portal pressure and hepatic fibrosis are pivotal parameters, both are determined using invasive procedures. Ultrasound (US) is a simple and non-invasive technique that is available for use worldwide in the abdominal field. Because of its safety and easy of use, contrast-enhanced US is one of the most frequently used tools in the management of liver tumors for the detection and characterization of lesions, assessment of malignancy grade, and evaluation of therapeutic effects. This wide range of applications drives the practical use of contrast-enhanced US for evaluation of the severity of portal hypertension and hepatic fibrosis. The present article reviews the recent progress in contrast-enhanced US for the assessment of portal hypertension and hepatic fibrosis.

Advances in the molecular diagnosis of hepatitis B infection: Providing insight into the next generation of disease

Hepatitis B virus (HBV) infection continues to represent a significant health threat, affecting over 400 million people worldwide. Historically, the diagnosis and treatment of chronic hepatitis B (CHB) relied in detection of the hepatitis B surface antigen (HBsAg) and more recently realtime polymerase chain reaction (PCR) analysis. The advent of novel technologies and equipment for the identification and staging of the different stages of HBV infection has resulted in dramatic changes to patient monitoring and management. Through the use of rapid, quantitative HBsAg immunoassays, it is now possible to predict the likelihood of patient response to treatment as well as the clinical course of disease. Ultradeep sequencing technologies (also known as next-generation sequencing) overcome many of the traditional limitations associated with population-based sequencing approaches, and have provided significant insight into the viral response to therapeutic intervention and the molecular pathogenesis of CHB. The authors discuss recent developments in the molecular diagnosis of HBV infection, as well as potential advantages and caveats resultant of this rapid progression of technology.

Development of non-alcoholic fatty liver disease scoring system among adult medical check-up patients: a large cross-sectional and prospective validation study

Background Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the community. However, NAFLD remains undiagnosed in most people with limited access to imaging facilities in most developing countries. Objective To examine the prevalence of NAFLD and to develop the risk scoring model for predicting the presence of NAFLD among adult medical check-up patients. Method A large prospective cross-sectional study was conducted among medical check-up patients who underwent transabdominal ultrasound examination between January and December 2013 in Medistra Hospital, Jakarta. Data were obtained from the patients’ medical records. Logistic regression analyses were undertaken to identify the best combination of risk factors for predicting fatty liver using the backward (likelihood ratio) approach. The adjusted odds ratio and 95% confidence interval were estimated using the logistic regression coefficient. The prediction model was assessed using the receiver operating characteristic curve and the Hosmer–Lemeshow goodness-of-fit test and was validated on a new, prospective cohort. Statistical analysis was done using SPSS version 17. Results A total of 1,054 cases was included in this study. Fatty liver was present in 538 (51.0%) patients. Bivariate analyses found associations among fatty liver and several risk factors. Six risk factors were incorporated to build the final prediction model. All scores were summed up to obtain the total score. A probability equation was developed by applying linear regression analysis on the total score. The prediction model had good diagnostic performance with an area under the receiver operating characteristic curve =0.833 (95% confidence interval =0.809–0.857). The Hosmer–Lemeshow goodness-of-fit P-value was 0.232, which indicated the appropriateness of the logistic regression model to predict fatty liver. On the validation set, the scoring system proved to be moderately accurate and can potentially be applied to larger population setting. Conclusion The presence of fatty liver in NAFLD patients can be predicted using our proposed fatty liver scoring system.

Clinical significance of hepatitis B virion and SVP productivity: relationships between intrahepatic and serum markers in chronic hepatitis B patients

Background Clinical use of hepatitis B viral (HBV) quantitative seromarker\s remains questionable since it is not precisely known whether they represent intrahepatic viral replication. Covalently closed circular DNA (cccDNA), relaxed circular DNA (rcDNA), and pregenomic RNA (pgRNA) are more likely to represent active HBV replication and their measurement can be used to derive virion productivity (VP; rcDNA/cccDNA), subviral particle (SVP) productivity (quantitative HBsAg/cccDNA), and replicative activity (RA; pgRNA/cccDNA). These can be used to compare relative HBV replication between HBeAg-negative and -positive patients. Objective To study the clinical significance of intrahepatic HBV replication phenomenon between HBeAg-negative and -positive patients and its correlation with quantitative HBV seromarkers. Method This was a prospective study between January 2010 and December 2011. Study subjects were naive chronic hepatitis B patients from Cipto Mangunkusumo and Medistra Hospitals. All patient samples underwent liver biochemistry and HBV seromarkers testing (HBeAg, quantitative HBsAg and HBV DNA levels), and patients underwent liver biopsy. Stored liver specimens were analysed for intrahepatic rcDNA, cccDNA, and pgRNA with quantification performed by real-time PCR. Comparison of HBV markers between HBsAg-positive and -negative patients was carried out using the Mann–Whitney U-test. Pearson’s correlation test was performed among HBV intrahepatic and seromarkers using their log-transformed values. Results A total of 104 patients were enrolled in this study; 54 (51.9%) were male. Patients’ mean age was 41.9 ± 11.63 years (range 19–70 years). Sixty-one patients (58.7%) were HBeAg-negative. All HBV markers were significantly higher in HBeAg-positive than HBeAg-negative patients, except for SVP productivity and RA. Serum HBV DNA was strongly correlated with intrahepatic total HBV DNA (r = 0.771), cccDNA (r = 0.774), and rcDNA (r = 0.780) while serum quantitative HBsAg showed only moderate correlation with intrahepatic total DNA (r = 0.671), cccDNA (r = 0.632), rcDNA (r = 0.675), and SVP productivity (r = 0.557). Conclusions Serum HBV DNA concentration and quantitative HBsAg might not accurately predict intrahepatic viral activity. Virion and SVP production do not occur in parallel with replicative activity.

Efficacy of Prothrombin Complex Concentrate Treatment in Patients with Liver Coagulopathy Who Underwent Various Invasive Hepatobiliary and Gastrointestinal Procedures

Background: Prothrombin complex concentrates (PCCs) containing prothrombin, factors VII, IX, and X, as well as the inhibitors protein C and S have been used as an emergent reversal for oral anticoagulation therapy. The use of PCCs in hepatobiliary disorder patients or patients with liver coagulopathy who need to undergo invasive procedures has not been well studied. Objective: To evaluate the efficacy of PCC treatment in order to control or prevent bleeding complications in patients with liver coagulopathy who undergo various invasive procedures. Methods: This was a prospective, open-label, non-randomized, before-and-after study in patients with hepatobiliary disorders who underwent invasive procedures accompanied by liver impairment and received PCC injection (Cofact®, Sanquin, The Netherlands). Patients with coagulopathy from various causes were recruited consecutively. Data collected were the episodes of bleeding, liver function test and the international normalized ratio (INR) before and after PCC therapy. The primary endpoint was INR change after treatment, while secondary endpoints included bleeding control and bleeding event after treatment. Results: Thirty patients (17 men, 13 women) were enrolled. Patients’ mean age was 57.0 + 15.5 years. Liver cirrhosis was found in 14 patients (46.7%). The procedures consisted of liver biopsy, liver abscess aspiration, abdominal paracentesis, therapeutic upper gastrointestinal endoscopy, abdominal surgery, endoscopic retrograde cholangiopancreatography and percutaneous transhepatic biliary drainage. After treatment, 25 patients (83.3%) showed a decreased median INR (from 1.6 to 1.3) (p < 0.001, Wilcoxon’s signed-rank test). Five patients failed to show INR reduction. No new bleeding event related to the invasive procedures was observed. Conclusion: PCC treatment is effective to control and prevent bleeding complications in patients with liver coagulopathy who undergo invasive procedures.

Choledocholithiasis during Pregnancy: Multimodal Approach Treatment

Pregnancy is an important risk factor for growth of choledochal stones. Since choledocholithiasis encountered during pregnancy, which is also a possible cause of pancreatitis and cholangitis, may be the reason for serious morbidity and mortality both for the mother and the fetus, it should be treated. In this article, the results and reliability of endoscopic retrograde cholangiopancreatography (ERCP) application on a pregnant woman accompanied with percutaneous biliary procedures are presented. We report a case of 33-year-old woman at 19 th week of gestation with cholestatic jaundice due to a common bile duct (CBD) stone managed by endoscopic retrograde cholangiopancreatography (ERCP). The patient had post ERCP pancreatitis which resolved with medical management. Percutaneous cholecystostomy was also performed to control source of infection in the gallbladder. ERCP is the first procedure that will be preferred in the treatment of choledocholithiasis in pregnancy with the right indications provided that proper precautions have been taken. Possible harmful effects of ionized radiation on fetus during fluoroscopy should be minimalized by giving in short periods and low doses. Keywords:

Hyperuricemia as an independent risk factor for non-alcoholic fatty liver disease (NAFLD) progression evaluated using controlled attenuation parameter-transient elastography: Lesson learnt from tertiary referral center

BACKGROUND AND AIM Hyperuricemia is one of the metabolic parameter which has been considered to play an important role in non-alcoholic fatty liver disease (NAFLD). However, there is still lack of studies about association between serum uric acid with liver disease progression in NAFLD. This study aimed to know the association between hyperuricemia with moderate to severe steatosis and significant fibrosis along with other metabolic factors in NAFLD patients evaluated using Controlled Attenuation Parameter (CAP) - Transient Elastography (TE). METHODS This is a prospective study in NAFLD patients who came to our tertiary referral center University hospital hepatobiliary outpatients clinic. All patients underwent metabolic parameters measurement including serum uric acid level and CAP-TE examination. Cutoff value used for significant liver fibrosis ≥7 kPa and ≥285 dB/m for moderate-severe steatosis. RESULTS Of 113 NAFLD patients, there were 45 patients with moderate-severe steatosis and 34 patients with significant fibrosis. Multivariate analysis showed only high level of fasting blood glucose (OR 2756; 95% CI 1.131-6.717) and low HDL level (OR 4.196, 95% CI 1.22-14.430) to be independent risk factors of moderate-severe steatosis. High level of fasting blood glucose (OR 3.98, 95% CI 1.105-14.389) and hyperuricemia (OR 2.501, 95% CI 1.095-5.714) were found to be independent risk factors for significant liver fibrosis. CONCLUSION Hyperuricemia is found to be an independent risk factor for significant liver fibrosis.

Non-alcoholic fatty pancreas disease as a risk factor for pancreatic cancer based on endoscopic ultrasound examination among pancreatic cancer patients: A single-center experience: NAFPD as a risk factor for pancreatic cancer

Non‐alcoholic fatty pancreas disease (NAFPD) is a disease that ranges from simple steatosis and can further lead to chronic pancreatitis and possible pancreatic cancer development. Its exact pathogenesis and impact on clinical practice are still largely unknown. Pancreatic cancer is still the most lethal malignancy in the world. Studies about the relationship between NAFPD and pancreatic cancer are still lacking. This study aims to find the possible role of endoscopic ultrasound (EUS) examination as a screening tool in NAFPD patients based on EUS examination among pancreatic cancer patients.