Risk of Hepatitis C Virus Transmission through Acupuncture: A Systematic Review and Meta-Analysis / 대한소화기학회지

Background/Aims@#Chronic hepatitis C is a major risk factor for liver cirrhosis, hepatocellular carcinoma, and hepatic failure. Although traditional practices, including acupuncture, tend to increase the risk of HCV infection, the association remains controversial. Therefore, the current meta-analytical study was undertaken to evaluate the risks of acupuncture and hepatitis C transmission. @*Methods@#Two researchers independently screened studies from the databases encompassing the period from inception to May 12, 2022. Baseline demographics, HCV transmission OR, and 95% CIs were extracted, pooled, and analyzed using random-effect models.Subgroup analyses utilizing study design and ethnicity were performed. Heterogeneity and publication bias were analyzed using the Higgins I2 test and funnel plots, respectively. @*Results@#In all, 28 studies with 194,826 participants (178,583 controls [91.7%] vs. 16,243 acupuncture users [8.3%]) were included in the final analysis. The pooled analysis showed that acupuncture users had a significantly higher HCV transmission rate than controls with heterogeneity (OR, 1.84 [1.46–2.32]; p<0.001; I2 =80%). In the subgroup analysis, both cross-sectional case-control (n=14; OR, 1.96 [1.47–2.61]; p<0.001; I2 =88%) and cross-sectional studies (n=12; OR, 1.85 [1.32–2.61]; p<0.001; I2 =0%) showed significantly higher HCV infection rates in the acupuncture group than in the control group. Both Asian and non-Asian acupuncture users showed a higher HCV transmission risk than the controls (all Ps <0.001). No significant publication bias was observed. @*Conclusions@#Our findings indicate that acupuncture increases the risk of HCV transmission. Due to HCV's contagiousness, unsafe medical and social practices (including acupuncture) should be performed with caution.

Therapeutic mechanisms and beneficial effects of non-antidiabetic drugs in chronic liver diseases

The global burden of chronic liver disease (CLD) is substantial. Due to the limited indication of and accessibility to antiviral therapy in viral hepatitis and lack of effective pharmacological treatment in nonalcoholic fatty liver disease, the beneficial effects of antidiabetics and non–antidiabetics in clinical practice have been continuously investigated in patients with CLD. In this narrative review, we focused on non-antidiabetic drugs, including ursodeoxycholic acid, silymarin, dimethyl4,4’-dimethoxy-5,6,5’,6’-dimethylenedixoybiphenyl-2,2’-dicarboxylate, L-ornithine L-aspartate, branched chain amino acids, statin, probiotics, vitamin E, and aspirin, and summarized their beneficial effects in CLD. Based on the antioxidant, anti-inflammatory properties, and regulatory functions in glucose or lipid metabolism, several non–antidiabetic drugs have shown beneficial effects in improving liver histology, aminotransferase level, and metabolic parameters and reducing risks of hepatocellular carcinoma and mortality, without significant safety concerns, in patients with CLD. Although the effect as the centerpiece management in patients with CLD is not robust, the use of these non-antidiabetic drugs might be potentially beneficial as an adjuvant or combined treatment strategy.

Independent Risk Factors for Hepatocellular Carcinoma Recurrence after Direct-Acting Antiviral Therapy in Patients with Chronic Hepatitis C

Background/Aims@#This study was performed to evaluate the efficacy of direct-acting antivirals (DAAs) in Korean patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) and to investigate the risk factors associated with HCC recurrence. @*Methods@#A total of 100 patients with HCV-related HCC, who were treated with DAAs between May 2015 and December 2016, were recruited from seven university hospitals in Korea. Claim data of 526 patients with HCC obtained from the Health Insurance Review and Assessment Service in South Korea were used for external validation of the results. @*Results@#Among the 100 patients, 88% achieved a sustained virological response (SVR) 12weeks after the end of DAA therapy (SVR12), and 37% experienced HCC recurrence after DAA therapy. Short last HCC treatment durability (<12 months) before DAA commencement was independently associated with HCC recurrence (hazard ratio [HR], 2.89; p=0.011). In the nationwide validation cohort, 20.3% of the patients experienced HCC recurrence. The last HCC treatment with a noncurative method, a short last HCC treatment durability (<12 months), and a longer total duration of HCC treatment (≥18 months) were independently related with HCC recurrence (HR3.73, p<0.001; HR 3.34, p<0.001; and HR 1.74, p=0.006; respectively). @*Conclusions@#DAA therapy showed an acceptable SVR12 rate in patients with HCV-related HCC. Short last HCC treatment durability (<12 months) was associated with HCC recurrence after DAA therapy. This finding suggests that the last HCC treatment durability is an important predictor of HCC recurrence after DAA therapy.

Independent Risk Factors for Hepatocellular Carcinoma Recurrence after Direct-Acting Antiviral Therapy in Patients with Chronic Hepatitis C

Background/Aims@#This study was performed to evaluate the efficacy of direct-acting antivirals (DAAs) in Korean patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) and to investigate the risk factors associated with HCC recurrence. @*Methods@#A total of 100 patients with HCV-related HCC, who were treated with DAAs between May 2015 and December 2016, were recruited from seven university hospitals in Korea. Claim data of 526 patients with HCC obtained from the Health Insurance Review and Assessment Service in South Korea were used for external validation of the results. @*Results@#Among the 100 patients, 88% achieved a sustained virological response (SVR) 12weeks after the end of DAA therapy (SVR12), and 37% experienced HCC recurrence after DAA therapy. Short last HCC treatment durability (<12 months) before DAA commencement was independently associated with HCC recurrence (hazard ratio [HR], 2.89; p=0.011). In the nationwide validation cohort, 20.3% of the patients experienced HCC recurrence. The last HCC treatment with a noncurative method, a short last HCC treatment durability (<12 months), and a longer total duration of HCC treatment (≥18 months) were independently related with HCC recurrence (HR3.73, p<0.001; HR 3.34, p<0.001; and HR 1.74, p=0.006; respectively). @*Conclusions@#DAA therapy showed an acceptable SVR12 rate in patients with HCV-related HCC. Short last HCC treatment durability (<12 months) was associated with HCC recurrence after DAA therapy. This finding suggests that the last HCC treatment durability is an important predictor of HCC recurrence after DAA therapy.

Long-term Nucleotide Analogue Treatment Has Higher Levels of Renal Toxicities than Does Entecavir in Patients with Chronic Hepatitis B

Background/Aims@#Renal toxicity is a concern in patients with chronic hepatitis B taking nucleotide analogues, such as adefovir (ADV) and tenofovir disoproxil fumarate (TDF). We sought to determine the long-term renal effects of nucleotide analogue treatment versus entecavir (ETV) treatment. @*Methods@#In this retrospective single-center study, we selected 87 patients who were treated with ADV and subsequently with TDF from June 2008 to December 2013. ETV-treated patients were matched by treatment duration. We analyzed the creatinine increase over 0.5 mg/dL, glomerular filtration rate (GFR) decrease over 25%, phosphorus decrease under 2.0 mg/dL, and dose reduction of antiviral agents. @*Results@#The median follow-up period was 60.0 months for both groups. The incidence of liver cirrhosis was higher in the ADVTDF group than in the ETV group (32.2% vs 74.7%, p<0.01).Creatinine increased in both groups during follow-up, but the difference was not significant (5.7% and 2.3%, p=0.44). In addition, GFR decreased more often in the ADV-TDF group than in the ETV group (31.0% and 14.9%, p=0.01). After multivariate Cox regression analysis, ADV-TDF treatment was significantly associated with a GFR decrease over 25% (hazard ratio, 2.10; 95% confidence interval, 1.08 to 4.10; p=0.03) after adjusting for the baseline GFR decrease. @*Conclusions@#Patients taking nucleotide analogues had a significantly higher number of renal events than did those taking ETV. Clinicians should be aware of the development of renal toxicity in this patient population. Further long-term studies are warranted.

Two-Dimensional-Shear Wave Elastography with a Propagation Map: Prospective Evaluation of Liver Fibrosis Using Histopathology as the Reference Standard

Objective@#The aim of this study was to prospectively evaluate whether liver stiffness (LS) assessments, obtained by twodimensional (2D)-shear wave elastography (SWE) with a propagation map, can evaluate liver fibrosis stage using histopathology as the reference standard. @*Materials and Methods@#We prospectively enrolled 123 patients who had undergone percutaneous liver biopsy from two tertiary referral hospitals. All patients underwent 2D-SWE examination prior to biopsy, and LS values (kilopascal [kPa]) were obtained. On histopathologic examination, fibrosis stage (F0–F4) and necroinflammatory activity grade (A0–A4) were assessed. Multivariate linear regression analysis was performed to determine the significant factors affecting the LS value.The diagnostic performance of the LS value for staging fibrosis was assessed using receiver operating characteristic (ROC) analysis, and the optimal cut-off value was determined by the Youden index. @*Results@#Reliable measurements of LS values were obtained in 114 patients (92.7%, 114/123). LS values obtained from 2D-SWE with the propagation map positively correlated with the progression of liver fibrosis reported from histopathology (p < 0.001). According to the multivariate linear regression analysis, fibrosis stage was the only factor significantly associated with LS (p < 0.001). The area under the ROC curve of LS from 2D-SWE with the propagation map was 0.773, 0.865, 0.946, and 0.950 for detecting F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The optimal cut-off LS values were 5.4, 7.8, 9.4, and 12.2 kPa for F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The corresponding sensitivity and specificity of the LS value for detecting cirrhosis were 90.9% and 88.4%, respectively. @*Conclusion@#The LS value obtained from 2D-SWE with a propagation map provides excellent diagnostic performance in evaluating liver fibrosis stage, determined by histopathology.

Two-Dimensional-Shear Wave Elastography with a Propagation Map: Prospective Evaluation of Liver Fibrosis Using Histopathology as the Reference Standard

Objective@#The aim of this study was to prospectively evaluate whether liver stiffness (LS) assessments, obtained by twodimensional (2D)-shear wave elastography (SWE) with a propagation map, can evaluate liver fibrosis stage using histopathology as the reference standard. @*Materials and Methods@#We prospectively enrolled 123 patients who had undergone percutaneous liver biopsy from two tertiary referral hospitals. All patients underwent 2D-SWE examination prior to biopsy, and LS values (kilopascal [kPa]) were obtained. On histopathologic examination, fibrosis stage (F0–F4) and necroinflammatory activity grade (A0–A4) were assessed. Multivariate linear regression analysis was performed to determine the significant factors affecting the LS value.The diagnostic performance of the LS value for staging fibrosis was assessed using receiver operating characteristic (ROC) analysis, and the optimal cut-off value was determined by the Youden index. @*Results@#Reliable measurements of LS values were obtained in 114 patients (92.7%, 114/123). LS values obtained from 2D-SWE with the propagation map positively correlated with the progression of liver fibrosis reported from histopathology (p < 0.001). According to the multivariate linear regression analysis, fibrosis stage was the only factor significantly associated with LS (p < 0.001). The area under the ROC curve of LS from 2D-SWE with the propagation map was 0.773, 0.865, 0.946, and 0.950 for detecting F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The optimal cut-off LS values were 5.4, 7.8, 9.4, and 12.2 kPa for F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The corresponding sensitivity and specificity of the LS value for detecting cirrhosis were 90.9% and 88.4%, respectively. @*Conclusion@#The LS value obtained from 2D-SWE with a propagation map provides excellent diagnostic performance in evaluating liver fibrosis stage, determined by histopathology.

Tenofovir and Entecavir Have Similar Renal Adverse Events on Hepatocellular Carcinoma Patients Treated with Transarterial Chemoembolization

BACKGROUND/AIMS: Tenofovir disoproxil fumarate (TDF) is potentially nephrotoxic in chronic hepatitis B patients. Hepatocellular carcinoma (HCC) patients treated using transarterial chemoembolization (TACE) are at an increased risk of renal injury. The aim of this study was to determine whether TDF is associated with more renal adverse events than entecavir (ETV) in HCC patients treated with TACE. METHODS: In this retrospective single-center study, we selected 53 HCC patients who were treated with TDF from January 2012 to July 2013 and had their first TACE procedure in the same period. These patients were matched by age and sex to patients treated with ETV. RESULTS: There were no significant differences in baseline characteristics, including HCC factors, and nephrotoxic drug use, between the two groups. The median follow-up period was 17.0 and 20.0 months for the TDF and ETV groups, respectively. There was no difference during the follow-up period between the TDF and ETV groups in the increase in creatinine over 0.5 mg/dL (17.0% and 17.0%, P=1.00, respectively) and the decrease in eGFR over 25% (43.4% and 41.5%, P=0.84, respectively). Multivariate analysis revealed that Child-Pugh class over B (hazard ratio [HR], 7.30; 95% confidence interval [CI] 2.79–19.10; P<0.01) was associated with increase in creatinine, and Child-Pugh class over B (HR, 82.74; 95% CI 12.31–555.83; P<0.01) and Barcelona-Clinic Liver Cancer stage over B (HR, 14.93; 95% CI 1.60–139.51; P=0.02) were associated with decrease in eGFR. CONCLUSIONS: TDF has comparable safety to that of ETV for HCC patients undergoing TACE.

Assessment of the Surveillance Interval at 1 Year after Curative Treatment in Hepatocellular Carcinoma: Risk Stratification

BACKGROUND/AIMS: Guidelines recommend surveillance for hepatocellular carcinoma (HCC) recurrence at 3-month intervals during the first year after curative treatment and 6-month intervals thereafter in all patients. This strategy does not reflect individual risk of recurrence. We aimed to stratify risk of recurrence to optimize surveillance intervals 1 year after treatment. METHODS: We retrospectively analyzed 1,316 HCC patients treated with resection/radiofrequency ablation at Barcelona Clinic Liver Cancer stage 0/ A. In patients without 1-year recurrence under 3-monthly surveillance, a new model for recurrence was developed using backward elimination methods: training (n=582)/ validation cohorts (n=291). Overall survival (OS) according to risk stratified by the new model was compared according to surveillance intervals: 3-monthly versus 6-monthly (n=401) after lead time bias correction and propensity-score matching analyses. RESULTS: Among patients without 1-year recurrence, age and international normalized ratio values were significant factors for recurrence (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.00 to 1.03; p=0.009 and HR, 5.63; 95% CI, 2.24 to 14.18; p < 0.001; respectively). High-risk patients stratified by the new model showed significantly higher recurrence rates than low-risk patients in the validation cohort (HR, 1.73; 95% CI, 1.18 to 2.53; p=0.005). After propensity-score matching between the 3-monthly and 6-monthly surveillance groups, OS in high-risk patients under 3-monthly surveillance was significantly higher than that under 6-monthly surveillance (p=0.04); however, OS in low-risk patients under 3-monthly surveillance was not significantly different from that under 6-monthly surveillance (p=0.17). CONCLUSIONS: In high-risk patients, 3-monthly surveillance can prolong survival compared to 6-monthly surveillance. However, in low-risk patients, 3-monthly surveillance might not be beneficial for survival compared to 6-monthly surveillance.

A Case of Hepatocellular Carcinoma with Recurrent Peritoneal Metastasis after Hepatectomy Who Showed Complete Response by Surgical Resection

Recurrence of hepatocellular carcinoma (HCC) after hepatic resection is quite common. Peritoneal recurrence has been considered incurable status and related to poor prognosis. Although peritoneal metastasectomy is a therapeutic option for some selected patients with a few peritoneal metastasis, the indication and therapeutic effect has not been clear. We report a case of a 61-year-old man achieving complete remission of recurrent peritoneal metastasis after repeated surgical resection by a multidisciplinary approach. Peritoneal metastasectomy might be a therapeutic option for selected patients with localized oligonodular peritoneal metastasis.

A Case of Hepatocellular Carcinoma in a Patient with Crohn's Disease / 대한내과학회지

Hepatocellular carcinomas (HCCs) in patients with Crohn's disease (CD) without underlying chronic hepatitis or liver cirrhosis are extremely rare. Previously reported cases occurred in patients who had developed CD at a young age and had been treated with immunosuppressive agents long-term. We herein report the first case of HCC in a 34-year-old patient with CD in Korea. The patient was treated with azathioprine for 14 years and had undergone repeated surgeries for CD. During the follow-up period, the patient was hospitalized for colon perforation and pericolic abscess formation. Computed tomography showed a liver mass, and HCC was diagnosed based on liver biopsy. The patient underwent right hemicolectomy for colon perforation and transcatheter arterial chemoembolization followed by radiofrequency ablation for the HCC. The present case is similar to previously reported cases with the exception of the liver pathology findings, which exhibited neither primary sclerosing cholangitis nor focal hepatic glycogenolysis.

Two Cases of Early Recurred Hepatocellular Carcinoma after Surgical Resection Which Showed Different Outcomes

Hepatocellular carcinoma (HCC) has poor prognosis, even after curative resection. Early recurrence after curative treatment is a major cause of the poor prognosis. Pathologic factors such as vessel invasion, satellite nodule, size of tumor and pathologic grade are prognostic factors predicting early recurrence and poor prognosis. We share our experience of two cases which both showed early recurrence after curative hepatic resection, but eventually demonstrated different prognosis. Since the most common cause of death after potentially curative treatment is tumor recurrence, suppression of tumor recurrence might be linked to survival gain. Currently, there is no adjuvant therapy for HCC endorsed by international guidelines. However, recent studies have shown that antiviral treatment for hepatitis B virus-related HCC and immunotherapy using autologous cytokine-induced killer cell reduced HCC recurrence. Further study is needed to select patients who will benefit from adjuvant treatments.

Transarterial Chemoembolization versus Radiofrequency Ablation for Small Hepatocellular Carcinomas with Discrepant Features on Computed Tomography and Magnetic Resonance Imaging

BACKGROUND/AIMS: This study compared the outcomes of patients with small hepatocellular carcinomas (HCCs) who were treated using transarterial chemoembolization (TACE) or radiofrequency ablation (RFA). METHODS: This was a post-hoc analysis of a prospective study that evaluated the diagnostic efficacy of magnetic resonance imaging (MRI) and computed tomography (CT). We analyzed 41 small hepatic nodules in 32 patients that showed typical radiologic hallmarks on both CT and gadoxate-enhanced MRI (typical nodules) and 25 small hepatic nodules from 22 patients that showed atypical radiologic hallmarks on CT and typical radiologic hallmarks on MRI (discrepant nodules). RESULTS: There were no significant differences in the baseline characteristics of the patients with typical and discrepant nodules. Complete response rates 1 month after TACE or RFA were 75.0% (18/24) and 94.1% (16/17; P=0.20), respectively, for the patients with typical nodules and 58.8% (10/17) and 100% (8/8; P=0.05), respectively, for the patients with discrepant nodules. Treatment failure rates after TACE or RFA were 33.3% (8/24) and 5.8% (1/17; P=0.15), respectively, for the patients with typical nodules and 47.0% (8/17) and 0.0% (0/8; P=0.02), respectively, for the patients with discrepant nodules. Among patients achieving complete response, there were no significant differences in the risk of marginal recurrence. CONCLUSIONS: RFA provided higher complete response rates and significantly lower treatment failure rates than TACE for patients with discrepant nodules of HCC. Therefore, a treatment modality such as RFA may be preferable for small HCCs which show discrepancy on two imaging modalities.

Disappearance of Intrahepatic Bile Duct Hepatocellular Carcinoma after Endoscopic Retrograde Cholangiopancreatography and Transarterial Chemoinfusion: A Case Report / 대한소화기학회지

Invasion of the bile duct by hepatocellular carcinoma (HCC), which is called intrahepatic bile duct HCC, is rare and has a poor prognosis. Early diagnosis and surgical resection is important for treatment. A 58-year-old man who underwent hepatic resection for HCC 4 years ago and received transarterial chemoembolization (TACE) 2 years after the operation for recurred HCC presented with jaundice. CT scan revealed a tumor in the common bile duct without intrahepatic lesion. Therefore, ERCP was done to perform biopsy and biliary drainage. Histological examination was compatible with hepatocellular carcinoma. However, the tumor could not be visualized at angiography and thus, only transarterial chemoinfusion was performed without embolization. The tumor had disappeared on follow-up CT scan, and the patient has been disease free for 23 months without evidence of recurrence. Herein, we report a case of intrahepatic bile duct HCC which disappeared after ERCP.

Usefulness of Routine Renal Sonography Screening for Healthy Infants with Isolated Single Umbilical Artery

PURPOSE: It is known that single umbilical artery is frequently associated with gastrointestinal or urogenital anomaly, however, routine renal sonography has been debated in healthy neonate with isolated single umbilical artery. This study is designed to determine the usefulness of routine renal sonography in apparently healthy infants with an isolated single umbilical artery. METHODS: Thirty healthy neonates with a single umbilical artery without a major anomaly from January 1995 to July 2002 were enrolled. The authors investigated the clinical background of babies and their mothers after renal sonography after 72 hours of age. When the abnormalities were found at the first renal sonography, the severity of hydronephrosis and degree of obstruction and renal function were analyzed by follow up renal sonography, voiding cystourethrography(VCUG) and technetium-99m-dimercaptosuccinic acid(DMSA) scan or technetium-99m-mercaptoacetyl-triglycerine (MAG3) scan. RESULTS: Among the 30 healthy patients with isolated single umbilical artery, five patients(16.7%) showed abnormalities on first renal sonography with one major(3.3%) and four(13.4%) minor renal anomaly(minimal or mild hydroneohrosis). One major renal anomaly(severe hydronephrosis) showed severe decreased renal function on MAG3 scan without reflux, and the other four minor regressed spontaneously on follow up study. CONCLUSION: The value of routine early renal sonograpy for detecting renal anomaly in healthy infants with an isolated single umbilical artery remained unclear because most of the anomalies would regress spontaneously in the follow up study.