Persistent hypoglycemia in patients with liver cancer.

Summary: Hypoglycemia is one of the paraneoplastic syndrome manifestations that arise from primary and secondary liver cancer. Hypoglycemia usually presents in the late stage of the disease and indicates a poor prognosis. This case series displays the characteristics profile of patients with primary and secondary liver cancer who are presented with hypoglycemia in a tertiary referral hospital in Indonesia. The study included 41 liver cancer patients who were presented with hypoglycemia. Hepatocellular carcinoma was diagnosed in 51.2% of patients, metastatic liver disease in 14.6% of patients, and undiagnosed liver cancer in 34.1% of patients. The mean age was 47.7 years with male predominance (65.9%). Jaundice was found in 58.5% and hepatomegaly in 70.7% of patients. The mean (± S.D.) initial blood glucose was 42.15 ± 17.11 mg/dL and the Child-Pugh score was 9.93 ± 2.11. Based on imaging, tumor diameter was 12.6 ± 6.9 cm, multiple (61%), and involving both lobes (61%). Treatments for hypoglycemia included oral/enteral feeding, intravenous dextrose, and steroids. No treatment was given for the cancer because all patients were in an advanced stage. The treatment resulted in 41.5% blood glucose being controlled, 56.1% refractory, and 2.4% persistent. Mortality was 70.7% and in average occurred 5.76 ± 4.99 days after hypoglycemia. The mainstay of treatment in these cases is treating the tumor with cytoreduction. However, it was difficult to do cytoreduction because the tumor was already in an advanced stage. Beneficial supportive treatments for maintaining normal blood glucose are frequent meals, dextrose infusion, steroids, and glucagon. Learning points: Hypoglycemia in liver cancer occurs due to the failure of the liver to fulfill body glucose demand because the liver parenchyma has been largely replaced by the tumor, in addition to the high production of insulin growth factor (IGF). Hypoglycemia is often caused by islet cell and non-islet cell tumors, with a higher occurrence in non-islet cell tumors due to paraneoplastic syndrome and the high metabolic requirements of the tumor. The mainstay of NICTH treatment is treating the tumor with cytoreduction. However, in an advanced stage, cytoreduction therapy is often challenging to conduct. Beneficial supportive treatments for controlling blood glucose are frequent meals, dextrose infusion, and the injection of steroids and glucagon. Steroids play a beneficial role in the treatment of persistent hypoglycemia in hepatocellular carcinoma by stimulating gluconeogenesis and increasing lipolysis. Steroids also have roles in the inhibition of peripheral glucose intake, suppression of big IGF-2 production, and modulation of the GH-IGF axis.

Indonesian consensus on systemic therapies for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a deadly cancer with a rising incidence in the last 20 years. Most patients are diagnosed late when curative treatment is no longer feasible. With the background of chronic liver disease in most patients, the management of HCC becomes more complicated, in which well-preserved liver function is a prerequisite for locoregional or systemic therapies. In 2008, sorafenib became the first systemic agent proven to provide survival benefit for patients with advanced-stage HCC. For nearly a decade, no treatment has succeeded in providing better results than sorafenib. However, numerous advances in systemic therapies have emerged in the last 5 years to fulfill the unmet needs of effective therapeutic options. Several agents have been approved for clinical use after positive results in phase III clinical trials, including lenvatinib, regorafenib, cabozantinib, ramucirumab, and lastly immune checkpoint inhibitor atezolizumab in combination with bevacizumab, a monoclonal antibody targeting the vascular endothelial growth factor. With various options available, knowledge on the clinical evidence of each drug, their safety profile, as well as the patient characteristics and preferences become mandatory in clinical decision making. The objective of this consensus is to help clinicians, health-care workers, and policy makers in providing best clinical care for HCC patients.

Assessment of Circulating Tumor Cells in Colorectal Cancer as an Adjunctive Non-invasive Diagnostic Method.

BACKGROUND: Colorectal cancer (CRC) is a significant contributor to cancer-related morbidity and mortality. Biopsy remains the gold standard for CRC diagnosis, but invasive testing may not be preferred as an initial diagnostic procedure. Therefore, alternative non-invasive approaches are needed. Circulating tumor cells (CTC) present in the bloodstream have great potential as a non-invasive diagnostic marker for CRC patients. This study aimed to assess the diagnostic potential of CTC in CRC as an adjunctive diagnostic method using a subjective manual identification method and laser capture microdissection at 40x magnification. METHODS: A cross-sectional study was conducted on adult patients suspected to have CRC at Dr. Cipto Mangunkusumo National General Hospital, Jakarta, between November 2020 and March 2021. CTC analysis was performed using the negative selection immunomagnetic method with Easysep™ and the CD44 mesenchymal tumor marker. The identification and quantification of CTC were conducted manually and subjectively, with three repetitions of cell counting per field of view at 40x magnification. RESULTS: Of 80 subjects, 77.5% were diagnosed with CRC, while 7.5% and 15% exhibited adenomatous polyps and inflammatory/hyperplastic polyps, respectively. The diagnostic analysis of CTC for detecting CRC (compared to polyps) using a CTC cutoff point of >1.5 cells/mL suggested sensitivity, specificity, and positive predictive value (PPV) of 50%, 88.89%, and 93.94%. Additionally, the negative predictive value (NPV), as well as the positive and negative likelihood ratio (PLR and NLR) were 34.04%, 4.5, and 0.56, respectively. The subjective manual identification and quantification of CTC were performed at 40x magnification using laser capture microdissection. CONCLUSION: This study assessed the diagnostic potential of CTC examination in CRC as an adjunctive diagnostic method using the subjective manual identification method and laser capture microdissection at 40x magnification. Despite the limitations associated with subjective cell counting, the results showed 50% sensitivity and 88.89% specificity in diagnosing CRC. Further studies are needed to optimize the manual identification process and validate the clinical utility of CTC analysis in CRC patients.

Overall Survival of Hepatocellular Carcinoma Patients Underwent Radiofrequency Ablation (RFA) Treatment: a Retrospective Cohort Study from Two Referral Hospitals in Indonesia.

BACKGROUND: Radiofrequency ablation (RFA) is one of the curative modality therapies commonly used for the early stage of HCC management. Although numerous studies have reported the outcome of RFA around the world, the data regarding the usage of RFA for the early and intermediate stage of HCC remains limited. Hence, the study aimed to report the survival rate of the early and intermediate stage HCC patients who underwent RFA in two tertiary referral hospitals in Jakarta, Indonesia. METHODS: A retrospective cohort study was conducted in Cipto Mangunkusumo and Medistra multicenter hospital in Jakarta, Indonesia. The patients with HCC BCLC A and B who underwent RFA treatments between January 2015 to December 2017 were recruited for the study. Baseline characteristics of patients were collected from the medical record. Survival analysis was calculated using the Kaplan Meier. p value result was obtained from the log-rank test. Sub-analysis of factors associated with the survival was also included in this study. RESULTS: There were 62 patients enrolled in this study (32.3% were BCLC A and 67.7% were BCLC B). Forty-six out of 62 patients (74.2%) were reported to have RFA as their first line of treatment, while 12 (25.8%) were reported to have a combination of RFA and other therapy modalities. All these patients were follow-up with an average duration of 27 months. The survival rate of liver cancer due to HCC for 12 and 36 months in patients who received RFA was 82.3% and 57.8%, respectively. Moreover, BCLC staging of liver cancer and response after RFA was significantly associated with survival. CONCLUSION: RFA still can be used as initial modality therapy nor combination with another therapy for the early and intermediate stage of HCC. BCLC staging and response after RFA had shown to be the independent factors related to survival.

Hepatitis C continuum of care: Experience of integrative hepatitis C treatment within a human immunodeficiency virus clinic in Indonesia.

INTRODUCTION: Direct-acting antiviral drugs (DAAs) have changed the paradigm of hepatitis C therapy for both HCV/HIV co-infected and HCV mono-infected patients. We aimed to describe the HCV continuum of care of HIV-infected patients treated in an HIV clinic after a free DAA program in Indonesia and identify factors correlated with sofosbuvir-daclatasvir (SOF-DCV) treatment failure. METHODS: We did a retrospective cohort study of adult HIV/HCV co-infected patients under routine HIV-care from November 2019 to April 2020 in the HIV integrated clinic of Cipto Mangunkusumo Hospital, Jakarta, Indonesia. We evaluated some factors correlated with sofosbuvir-daclatasvir treatment failure: gender, diabetes mellitus, previous IFN failure, cirrhosis, concomitant ribavirin use, high baseline HCV-RNA, and low CD4 cell count. RESULTS AND DISCUSSION: Overall, 640 anti-HCV positive patients were included in the study. Most of them were male (88.3%) and former intravenous drug users (76.6%) with a mean age of 40.95 (SD 4.60) years old. Numbers and percentages for the stages of the HCV continuum of care were as follows: HCV-RNA tested (411; 64.2%), pre-therapeutic evaluation done (271; 42.3%), HCV treatment initiated (210; 32.8%), HCV treatment completed (207; 32.2%), but only 178 of these patients had follow-up HCV-RNA tests to allow SVR assessment; and finally SVR12 achieved (178; 27.8%). For the 184 who completed SOF-DCV treatment, SVR12 was achieved by 95.7%. In multivariate analysis, diabetes mellitus remained a significant factor correlated with SOF-DCV treatment failure (adjusted RR 17.0, 95%CI: 3.28-88.23, p = 0.001). CONCLUSIONS: This study found that in the HCV continuum of care for HIV/HCV co-infected patients, gaps still exist at all stages. As the most commonly used DAA combination, sofosbuvir daclatasvir treatment proved to be effective and well-tolerated in HIV/HCV co-infected patients. Diabetes mellitus was significant factor correlated with not achieving SVR12 in this population.

Impact of sofosbuvir and daclastavir on health-related quality of life in patients co-infected with hepatitis C and human immunodeficiency virus.

BACKGROUND: We conducted a real-life study of health-related quality of life (HRQoL) transformation before and 12 weeks after sofosbuvir and daclatasvir therapy in HCV/HIV co-infected patients. Factors related to the significant changes of each HRQoL domain/item were also evaluated. METHODS: A prospective study was performed in the HIV integrated clinic at Cipto Mangunkusumo Hospital, Jakarta. HCV/HIV co-infected patients who started sofosbuvir and daclatasvir from government free DAA program in 2017-2019. WHOQoL-HIV BREF and RAND SF-36 questionnaires were recorded at baseline and post-treatment week 12. RESULTS: 145 patients with mean age of 37.8 years (SD = 4.2) were included in the analysis. Most of patients were male (89%), previous IVDU (89%), active smoker (50.4%) and non-cirrhosis (80%). SVR12 was achieved in 95.5% of patients. Sofosbuvir and daclatasvir treatments showed positive impacts on 2 domains and 2 other items of WHOQoL-HIV BREF and 2 domains and 1 item of SF-36. Predicting factors of significant increase in each domain/item were: male and normal body mass index (BMI) for level of independence (RR 4.01,95% CI 1.09-14.74 and 4.80,95% CI 1.79-12.81); higher HCV-RNA for overall perception of QoL (RR 0.42,95% CI 0.18-0.94); non-smoking status for overall perception of health (RR 0.32,95% CI 0.15-0.66); male and fibrosis stage 0-1 for general health (RR 6.21,95% CI 1.69-22.88 and 2.86,95% CI 1.16-7.00); and the use of NNRTI-based ART (RR 5.23, 95% CI 1.16-23.65). Spiritual/personal belief decline was predicted by non-smoking status (RR 0.46, 95% CI 0.23-0.95). Treatment success was not associated with any changes of HR-QoL domain/item. CONCLUSIONS: HCV/HIV co-infected patients were successfully treated with sofosbuvir and daclatasvir and experienced improvement of HRQoL 12 weeks after treatment completion.

Clinical significance of isolated gastric varices in liver cirrhotic patients: A single-referral-centre retrospective cohort study.

INTRODUCTION: Gastric varices (GVs) occur in 10-30% of liver cirrhotic patients, with a mortality rate of up to 45%. Rupture of isolated GVs (IGVs) is less prevalent but often results in more severe hemorrhage and a higher risk of mortality than rupture of esophageal varices (EVs). However, there is no clear consensus yet about the optimal management for incidentally discovered IGVs. OBJECTIVE: To determine the clinical significance of IGVs in liver cirrhotic patients. METHODS: This was a retrospective cohort endoscopy database study within a 2-year period (2016-2017). All study subjects were liver cirrhotic patients with OVs or GVs. The exclusion criteria were noncirrhotic portal hypertension, presence of malignancy, absence of varices, and incomplete data. Statistical analysis was performed using IBM SPSS 23. RESULTS: A total of 153 patients were included in this study. IGVs were found in 13 (8.49%) patients, whereas OVs were found in 112 (73.20%) patients and gastro-OVs were found in 28 (18.30%) patients. Child-Pugh class C (CP C) score was the strongest independent risk factor for variceal bleeding in bivariate analysis (hazard ratio [HR]: 10.21, 95% confidence interval [CI]: 4.15-25.12, P = 0.001) and multivariate analysis (HR: 12.49, 95% CI: 4.95-31.54, P 0.001); however, the presence of IGVs was not an independent risk factor. CP C score was also the only significant risk factor associated with 1-year mortality in liver cirrhotic patients on multivariate analysis (HR: 26.77, 95% CI: 6.01-119.34, P 0.001). CONCLUSION: The presence of IGVs has no clinical significance in the occurrence of 1-year rebleeding and in patient survival.

Diagnostic performance of APRI and FIB-4 for confirming cirrhosis in Indonesian HIV/HCV co-infected patients.

BACKGROUND: After successful of antiretroviral therapy, highly effective direct acting antiviral (DAA) make HCV elimination reasonable in HIV/HCV co-infected patients. However, in achieving this target, there are still barriers to start DAA treatment, particularly in the area of liver fibrosis assessment that determine the duration of therapy. We aimed to assess the diagnostic performance of APRI and FIB-4 for diagnosing cirrhosis in HIV/HCV co-infected patients using hepatic transient elastography (TE) as gold standard. METHOD: This is a retrospective study on HIV/HCV co-infected patients who concomitantly performed hepatic TE measurement, APRI, and FIB-4 evaluation before HCV treatment initiation at a tertiary hospital in Jakarta from 2014 to 2019. Sensitivity, specificity and diagnostic accuracy of indirect biomarkers for liver stiffness measurement (LSM) ≥ 12.5 kPa was determined by receiver operator characteristics curves. RESULTS: 223 HIV/HCV co-infected patients on stable antiretroviral therapy were included, of whom 91.5% were male with mean age of 37 (SD 5) years. Only 28.7% of patients were classified as cirrhosis (F4). Using TE as gold standard (≥12.5 kPa), the low threshold of APRI (1) had specificity 95%, sensitivity 48.4%, correctly classified 81.6% of patients, with moderate performance, AUC at 0.72 (95% CI 0.63-0.80). The optimal cut-off of FIB-4 was 1.66 [specificity 92.5%, sensitivity 53.1%, AUC at 0.73 (95% CI 0.65-0.81)] and correctly classified 81.1% of the patients. CONCLUSION: APRI score ≥ 1 and FIB-4 score ≥ 1.66 had moderate performance with high specificity in diagnosing cirrhosis. These biochemical markers could be used while TE is not available.

Risk factors of mortality in the patients with hepatocellular carcinoma: A multicenter study in Indonesia.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is considered a significant burden, and its associated rate of mortality is increasing. Therefore, a population-based cancer registry is considered an essential element in the baseline and comprehensive analysis of the risk factors associated with HCC. We present a multicenter analysis of HCC registry from 2 hospitals in Indonesia. METHODS: We performed a follow-up on patients with HCC who were admitted between January 2015 and November 2017 in Cipto Mangunkusumo National General Hospital and Dharmais Hospital, Jakarta, Indonesia. Patient's death was considered the primary outcome of the study. A multivariate analysis was conducted using logistic regression, and odds ratio (OR) with 95% confidence intervals (CIs) were calculated. RESULTS: A total of 282 patients with HCC included. At the last follow-up, 136 (48.2%) patients had died. Mortality rate was not significantly affected by sex, age, etiology, the presence of cirrhosis, nor surveillance of HCC. Based on the Child-Pugh (CP) classification, the OR increased progressively in CP C patients (OR 1.95; 95% CI 1.08-3.53; P = 0.026). The progressive increase was also found in patients with a higher Barcelona Clinic Liver Cancer stage, and the OR for CP C and D patients were 3.50 (95% CI 1.18-10.38; P = 0.024) and 3.41 (95% CI 1.02-11.41; P = 0.047), respectively. Supportive treatment was the most common treatment modality with an OR of 2.17 (95% CI 1.14-4.16; P = 0.019), and it was associated with the mortality rate of HCC. CONCLUSIONS: The CP classification, Barcelona Clinic Liver Cancer staging system, and treatment modality might predict mortality in patients with HCC. Moreover, other parameters must be further evaluated.

Palliative Endoscopic Ultrasound Biliary Drainage for Advanced Malignant Biliary Obstruction: Should It Replace the Percutaneous Approach?

Endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic biliary drainage (PTBD) are the standard of care in malignant biliary obstruction cases. Recently, endoscopic ultrasound-guided biliary drainage (EUS-BD) has been widely used after unsuccessful ERCP. However, the patient's clinical impact of EUS-BD over PTBD is still not obvious. Therefore, this case series study aims to evaluate the clinical outcomes of patients with advanced malignant biliary obstruction who underwent EUS-BD after failed ERCP. A retrospective database study was performed between January 2016 and June 2018 in patients with advanced malignant biliary obstruction. Patients were consecutively enrolled without randomization. Treatment options consisted of ERCP and PTBD or EUS-BD if ERCP failed. Based on 144 biliary obstruction cases, 38 patients were enrolled; 24 (63.2%) were men. The patients' mean age was 66.8 ± 12.36 years. The most common cause of malignant biliary obstruction was pancreatic cancer (44.7%). Biliary drainage was achieved by ERCP (39.5%), PTBD (39.5%), and EUS-BD (21.1%). The technical success rate was 86.7% by PTBD and 87.5% by EUS-BD (p = 1.000), while the clinical success rate was 93.3% by PTBD and 62.5% by EUS-BD (p = 0.500). The median survival in patients who underwent PTBD versus those wo underwent EUS-BD was 11 versus 3 months (log-rank p = 0.455). In conclusion, there is no significant advantage of EUS-BD when compared to PTBD in terms of clinical success and survival benefit in advanced malignant biliary obstruction.

The role of Small Intestinal Bacterial Overgrowth (SIBO) in Non-alcoholic Fatty Liver Disease (NAFLD) patients evaluated using Controlled Attenuation Parameter (CAP) Transient Elastography (TE): a tertiary referral center experience.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an emerging disease, where it can progress to non-alcoholic steatohepatitis (NASH) and lead to liver cirrhosis or liver cancer. Small intestinal bacterial overgrowth (SIBO) has been hypothesized to play an important role in NAFLD development and progression, however, there is still conflicting data about this phenomenon. Transient Elastography (TE) examination using controlled attenuation parameter (CAP) has been validated for liver disease progression assessment in NAFLD. It is non-invasive method and easy to perform in clinical practice. Therefore, we would like to know the role of SIBO in NAFLD and its possible impact on disease progression. METHODS: A cross-sectional design study performed at outpatient's Hepatobiliary clinic at tertiary referral university hospital in Jakarta. All recruited study subjects based on inclusions criteria underwent laboratory examination, transabdominal ultrasound examination, CAP-TE 502 (by Echosens, France), and glucose hydrogen breath test (GHBT) using portable hydrogen breath test apparatus (Gastro+™ Gastrolyzer by Bedfont Scientific Ltd). Stool sample examination was performed using RT-PCR. RESULTS: This study recruited 160 subjects with median age of 58 (22-78) years and 108 (67.5%) of them are female. SIBO (65,5%), DM (70.8%), dyslipidemia (75.2%), obesity (76.6%), and metabolic syndrome (73%) were more prevalent in NAFLD than non-NAFLD population. Bivariate analysis showed no significant association between SIBO and NAFLD development (p = 0.191; PR 0.871; CI 95% [0.306-1.269]). SIBO was also not associated with significant hepatic steatosis (p = 0.951; PR = 0.951; CI 95% [0.452-2.239]) and fibrosis (p = 0.371; PR = 1.369; CI 95% [0.608-3.772]). However, the presence of central obesity has significantly associated with the presence of SIBO (p = 0.001; PR = 0.378; CI 95% [0.021-0.478]). Based on stool sample analysis from 60 NAFLD patients, there is a significant correlation using Spearmen test between the presence of Bacteroides and the stage of fibrosis (p .037). Further analysis between obese NAFLD patients and non-obese NAFLD patients showing that there is a significant decrease of Bifidobacteria (p .047) and Lactobacillus (p .038) in obese NAFLD patients and a tendency of increase Bacteroides in obese NAFLD patients (p .572). CONCLUSIONS: SIBO is not associated with NAFLD development and progression.

Complete Remission after Sequential Therapy of Drug Eluting Beads Transarterial Chemoembolization and Liver Resection in Large Solitary Nodule Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most prevalent and the second highest cause of death among cancer. The treatment of large solitary nodule HCC is still challenging. Transarterial chemoembolization (TACE) and liver resection are two modalities of therapy in HCC management. However, recurrence rate from each therapy is relatively high. We report a case of 46-year-old man diagnosed with large solitary nodule HCC, who was treated with drug eluting bead TACE (DEB-TACE) prior to liver resection. Studies about this combination are still limited and showed various results.

Therapeutic Interventional Endoscopic Ultrasound Based on Rare Cases in Indonesia: A Single-Center Experience in Unselected Patients.

BACKGROUND: Endoscopic ultrasound (EUS) is still not widely available and has a barrier in most Southeast Asian countries due to lack of training program, high cost, and hospital investment. In this study, we would like to show the impact of therapeutic interventional EUS procedures in gastroenterology practice in Indonesia, which represents the biggest Southeast Asian country. METHODS: Patients who underwent interventional EUS procedure in Medistra Hospital were prospectively recruited within 1 year. RESULTS: Of 147 patients who underwent EUS procedures, 39 patients underwent fine needle aspiration. Most of the cases suffered from pancreatic cancer (47.5%) followed by ampullary cancer (20%), gastric subepithelial mass (10%), and other conditions. There were 4 rare cases that underwent therapeutic interventional EUS procedures. Patients with large mesenteric cyst attached to the gastric wall and large left liver lobe cyst with gastric compression who were previously suspected with gastrointestinal stromal tumor were successfully managed by cyst aspiration. One patient with a large pseudocyst due to chronic pancreatitis was successfully managed by plastic stent placement. Another patient with duodenal duplication cyst causing duodenal obstruction was managed by inserting a plastic stent through the cyst. No complications were observed during and after the therapeutic EUS procedures. CONCLUSIONS: Innovation in interventional EUS has a high impact in gastroenterology practice as well as in a developing country like Indonesia, which represents the biggest Southeast Asian country. Further developments are needed regarding the cost, investment, and especially the necessary training curriculum to make this technology available in tertiary referral centers.

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.