The efficacy of treatment for hepatocellular carcinoma in elderly patients

Background@#/Aim: Despite the increasing proportion of elderly patients with hepatocellular carcinoma (HCC) over time, treatment efficacy in this population is not well established. @*Methods@#Data collected from the Korean Primary Liver Cancer Registry, a representative cohort of patients newly diagnosed with HCC in Korea between 2008 and 2017, were analyzed. Overall survival (OS) according to tumor stage and treatment modality was compared between elderly and non-elderly patients with HCC. @*Results@#Among 15,186 study patients, 5,829 (38.4%) were elderly. A larger proportion of elderly patients did not receive any treatment for HCC than non-elderly patients (25.2% vs. 16.7%). However, OS was significantly better in elderly patients who received treatment compared to those who did not (median, 38.6 vs. 22.3 months; P0.05). After IPTW, in intermediate-stage HCC, surgery (median, 66.0 vs. 90.3 months) and transarterial therapy (median, 36.5 vs. 37.2 months), and in advanced-stage HCC, transarterial (median, 25.3 vs. 26.3 months) and systemic therapy (median, 25.3 vs. 26.3 months) yielded comparable OS between the elderly and non-elderly HCC patients (all P>0.05). @*Conclusions@#Personalized treatments tailored to individual patients can improve the prognosis of elderly patients with HCC to a level comparable to that of non-elderly patients.

A Study of Retinal and Choroidal Vessel Changes in Chronic Alcoholics

Purpose@#To compare the retinal and choroidal vessels of chronic alcoholics with non-alcoholics. @*Methods@#This study included alcohol-associated liver disease (ALD) patients admitted between December 2020 and October 2021, along with age-matched controls. Retinal and choroidal vessel densities, measured using image binarization at the superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris, and choroidal layers, were compared between ALD patients and controls. Correlations between clinical parameters and vessel densities in ALD patients were also analyzed. @*Results@#Vessel densities at SCP, DCP, choriocapillaris, and choroidal layers were not significantly different between controls and ALD patients (p = 0.496, 0.988, 0.909, and 0.317, respectively). Platelet time and international normalized ratio (INR) were positively correlated with SCP density in ALD patients (r = 0.393 and 0.393; p = 0.015 and 0.015, respectively). @*Conclusions@#ALD does not significantly affect vessel densities in the retina and choroid. The positive correlations of platelet time and INR with SCP may be related to vessel dilatation, but they require further investigation.

Anti-fibrotic effects of branched-chain amino acids on hepatic stellate cells

Background/Aims@#Patients with liver cirrhosis (LC) have low levels of branchedchain amino acids (BCAAs). There is accumulating evidence that BCAAs have anti- fibrotic effects in cirrhosis. This study is aimed to evaluate the effect of BCAAs on the function and phenotype of activated hepatic stellate cells (HSCs). @*Methods@#LX-2, an immortalized human stellate cell line, was used in in vitro experiments. LX-2 cells were exposed to transforming growth factor β1 (TGF-β1) and BCAAs or to valine, leucine, and isoleucine, which are components of BCAAs. Activation of the TGF-β signaling pathway in LX-2 cells was observed using real- time quantitative polymerase chain reaction and Western blotting. @*Results@#The increased expression of snail family transcriptional repressor 1 (SNAI1) was observed in LX-2 cells activated by TGF-β1. After BCAA treatment, its expression was significantly decreased at the mRNA level. The increased expression of Col1α1 and TIMP2 at the mRNA level and alpha smooth muscle actin at the protein level in activated LX-2 cells decreased after BCAA treatment. Among the BCAA components, leucine and valine significantly abrogated TGF-β-induced activation of LX-2 cells. BCAA treatment led to the decreased phosphorylation of Smad2 and p38 proteins, which are markers for Smad and Smad-independent p38 mitogen-activated protein kinase signaling pathways, respectively. @*Conclusions@#BCAA treatment can improve hepatic fibrosis by directly affecting the activated state of hepatic stellate cells through inhibition of the TGF-β signaling pathway. Among BCAA components, leucine and valine mainly abrogated TGF-β-induced activation of HSCs. Our results suggest that BCAA may be used to attenuate the progression of liver fibrosis.

The role of transjugular intrahepatic portosystemic shunt in patients with portal hypertension: Advantages and pitfalls

Transjugular intrahepatic portosystemic shunt (TIPS) is an effective interventional procedure to relieve portal hypertension, which is a main mechanism for the development of complications of liver cirrhosis (LC), such as variceal hemorrhage, ascites, and hepatorenal syndrome. However, the high incidence of adverse events after TIPS implementation limits its application in clinical practice. Esophageal variceal hemorrhage is one of the major indications for TIPS. Recently, preemptively performed TIPS has been recommended, as several studies have shown that TIPS significantly reduced mortality as well as rebleeding or failure to control bleeding in patients who are at high risk of treatment failure for bleeding control with endoscopic variceal ligation and vasoactive drugs. Meanwhile, recurrent ascites is another indication for TIPS with a proven survival benefit. TIPS may also be considered as an effective treatment for other LC complications, usually as an alternative therapy. Although there are concerns about the development of hepatic encephalopathy and hepatic dysfunction after TIPS implementation, careful patient selection using prognostic scores can lead to excellent outcomes. Assessments of cardiac and renal function prior to TIPS may also be considered to improve patient prognosis.

Effect of antiviral therapy in reducing perinatal transmission of hepatitis B virus and maternal outcomes after discontinuing them

BACKGROUND/AIMS: There have been numerous efforts to reduce mother-to-child transmission (MTCT) of hepatitis B virus (HBV) with antiviral agents during pregnancy. However, there are limited data regarding the outcomes of pregnant women after delivery. This study was performed to evaluate the efficacy of antiviral agents in preventing MTCT of HBV and maternal long-term outcomes. METHODS: The HBV-infected pregnant women treated with antiviral agents to prevent MTCT were retrospectively reviewed. Forty-one pregnant women who received telbivudine or tenofovir during late pregnancy (28-34 week) were analyzed. Hepatitis B virus surface antibody (HBsAb) positivity was tested in 43 infants after 7 months of birth. Eleven mothers were followed >1 year after delivery. RESULTS: The mean HBV DNA titer before antiviral therapy was 8.67 (6.60–9.49) log copies/mL, and the median age at delivery was 32 years (range, 22–40). Eleven patients were treated with tenofovir and 30 with telbivudine. The median duration was 57 days (range, 23–100), and the median HBV DNA titer at birth was 5.06 log copies/mL (range, 2.06–6.50). Antiviral treatments were associated with significant HBV DNA reduction (P 12 months, and an antiviral agent was administered. CONCLUSIONS: Antiviral treatment during late pregnancy effectively reduced MTCT. Long-term follow-up should be required in such cases. In addition, given that maternal biochemical flare occurred in 18% of mothers, re-administration of antiviral agents might be required.

A Case of Sarcomatoid Cholangiocarcinoma Which Developed at the Site Previously Treated by Transarterial Chemoembolization

Intrahepatic sarcomatoid carcinoma is a rare tumor with poor prognosis due to its highly invasive and metastatic nature and difficulty for early detection. The most common form of intrahepatic sarcomatoid carcinoma is the sarcomatoid hepatocellular carcinoma, the development of which is usually associated with previous treatment for hepatocellular carcinoma. In contrast, sarcomatoid cholangiocarcinoma is extremely rare and results from spontaneous sarcomatoid transformation during the development of tumor. Here, we report a case of sarcomatoid cholangiocarcinoma, in a 58-year-old male, which developed at the site of previous treatment for hepatocellular carcinoma. A 9 × 7 cm sized tumor which had not been detected in the computed tomography exam 3 months before diagnosis was newly observed. The tumor rapidly progressed and the patient died only 31 days after the diagnosis.

A comparative study of sorafenib and metronomic chemotherapy for Barcelona Clinic Liver Cancer-stage C hepatocellular carcinoma with poor liver function

BACKGROUND/AIMS: Metronomic chemotherapy (MET) is frequently administered in comparatively low doses as a continuous chemotherapeutic agent. The aim of this study was to evaluate the feasibility and overall survival (OS) of MET compared to sorafenib for advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). METHODS: A total of 54 patients with advanced HCC and PVTT who had undergone MET were analyzed between 2005 and 2013. A total of 53 patients who had undergone sorafenib therapy were analyzed as the control group. The primary endpoint of this study was OS. RESULTS: The median number of MET cycles was two (1-15). The OS values for the MET group and sorafenib group were 158 days (132-184) and 117 days (92-142), respectively (P=0.029). The Cox proportional-hazard model showed that a higher risk of death was correlated with higher serum alpha fetoprotein level (≥400 mg/dL, hazard ratio [HR]=1.680, P=0.014) and Child-Pugh class B (HR=1.856, P=0.008). CONCLUSIONS: MET was associated with more favorable outcomes in terms of overall survival than was sorafenib in patients with advanced HCC with PVTT, especially in patients with poor liver function. Therefore, MET can be considered as a treatment option in patients with advanced HCC with PVTT and poor liver function.

Reactivation of Hepatitis C Virus and Its Clinical Outcomes in Patients Treated with Systemic Chemotherapy or Immunosuppressive Therapy

BACKGROUND/AIMS: According to the results of several studies, the outcome of hepatitis C virus (HCV) reactivation is not as severe as the outcome of hepatitis B virus reactivation. The aim of this study was to evaluate the effect of pharmacological immunosuppression on HCV reactivation. METHODS: The medical records of patients who underwent systemic chemotherapy, corticosteroid therapy, or other immunosuppressive therapies between January 2008 and March 2015 were reviewed. Subsequently, 202 patients who were seropositive for the anti-HCV antibody were enrolled. Exclusion criteria were: unavailability of data on HCV RNA levels, a history of treatment for chronic hepatitis C, and the presence of liver diseases other than a chronic HCV infection. RESULTS: Among the 120 patients enrolled in this study, hepatitis was present in 46 patients (38%). None of the patients were diagnosed with severe hepatitis. Enhanced replication of HCV was noted in nine (27%) of the 33 patients who had data available on both basal and follow-up HCV RNA loads. Reappearance of the HCV RNA from an undetectable state did not occur after treatment. The cumulative rate of enhanced HCV replication was 23% at 1 year and 30% at 2 years. CONCLUSIONS: Although enhanced HCV replication is relatively common in HCV-infected patients treated with chemotherapy or immunosuppressive therapy, it does not lead to serious sequelae.

A Case of Complete Response by Multidisciplinary Management in a Patient with Solitary Bone Metastasis after Curative Resection of Hepatocellular Carcinoma

Despite recent advances in the treatment of hepatocellular carcinoma (HCC), the prognosis of patients with extrahepatic metastasis from HCC still remains dismal. The current study presents a case of HCC that was metastatic to the pelvis and describes successful treatment with multidisciplinary approach to the skeletal metastasis. The patient was a 67-year-old male who presented with right pelvic pain 28 months following right hepatectomy for HCC. Computed tomography and magnetic resonance imaging indicated a solitary bone metastasis without intrahepatic recurrence. Complete response was achieved with multidisciplinary management including sorafenib, transarterial embolization, surgery to remove the metastatic mass and radiotherapy after surgery. A post-operative follow-up 15 months later found that the patient remained in good health with maintained complete response. This case suggests that a multidisciplinary approach can achieve long-term cancer-free survival and prolonged life expectancy beyond palliative care for patients with solitary bone metastasis after curative surgery for HCC.

Efficacy and safety of daclatasvir and asunaprevir for hepatitis C virus genotype 1b infection

BACKGROUND/AIMS: The treatment strategy for hepatitis C virus (HCV) has been changing rapidly since the introduction of direct-acting antivirals such as daclatasvir (DCV) and asunaprevir (ASV). We evaluated the efficacy and safety of DCV and ASV for HCV in real-life practice. METHODS: Patients were treated with 60 mg of DCV once daily plus 200 mg of ASV twice daily for 24 weeks, and followed for 12 weeks. The primary endpoint was a sustained virological response at 12 weeks after treatment (SVR12) and safety. RESULTS: This retrospective study included eight patients with chronic HCV genotype 1b infection. All of the enrolled patients were diagnosed with liver cirrhosis, and their mean age was 65.75 years. One patient was a nonresponder and two patients relapsed with previous pegylated interferon (PegIFN) and ribavirin (RBV) treatment. None of the patient showed NS5A mutation. An SVR12 was achieved in 88% of cases by the DCV and ASV combination therapy. The serum transaminase level and the aspartate-aminotransferase-to-platelet ratio were improved after the treatment. DCV and ASV were well tolerated in most of the patients, with treatment discontinuation due to adverse events (elevated liver enzyme and decompensation) occurring in two patients. CONCLUSIONS: In this study, combination of DCV and ASV treatment achieved a high sustained virological response with few adverse events even in those with cirrhosis, advanced age, and nonresponse/relapse to previous interferon-based therapy. Close monitoring of safety issues may be necessary when treating chronic HCV patients receiving DCV and ASV, especially in older patient and those with cirrhosis.

Comparative Study between Metronomic Chemotherapy and Transarterial Chemoembolization in Patients with Child-Pugh Class B Advanced Hepatocellular Carcinoma

BACKGROUND/AIMS: Metronomic (MET) chemotherapy is a treatment characterized by frequent infusion of low doses of chemotherapeutic agent without extended break. The aim of this study is to evaluate the efficacy of MET chemotherapy compared with transarterial chemoembolization (TACE) in patients with child B class advanced hepatocellular carcinoma (HCC). METHODS: Seventy-three patients with child B class advanced HCC were analyzed between April, 2007 and August, 2013 according to two treatment groups: (i) MET chemotherapy group (n=43, Epirubicin 35 mg/body surface area [BSA] every 4 weeks, and cisplatin 15 mg/BSA and 5-fluorouracil 50 mg/BSA weekly for 3 weeks) via an implantable port system with 1 week break. (ii) TACE group (n=30, Adriamycin 20-50 mg) every 4 weeks. Primary endpoint was overall survival (OS). RESULTS: The median survival times in the MET and TACE groups were 4.5 months and 3.1 months, respectively. The overall survival rate showed significantly better in the MET treatment group than in the TACE group (P=0.039). When the factors affecting patient OS were analyzed, MET chemotherapy (P=0.038, hazard ratio {HR} 0.538 [95% confidence interval {CI} 0.299-0.967]) was independently associated with OS. Larger maximal tumor size, extrahepatic metastasis and advanced stage also were significant factors for OS (P=0.009, HR 1.064 [95% CI 1.014-16.064]; P=0.014, HR 2.120 [95% CI 1.164-3.861]; P=0.019, HR 2.046 [95% CI 1.125-3.720], respectively). CONCLUSIONS: MET chemotherapy showed survival benefit than TACE in patients with child class B advanced HCC. Therefore, MET chemotherapy may be considered as a treatment option for advanced HCC with poor liver function.

A Fatal Spontaneous Gas Gangrene due to Clostridium perfringens during Neutropenia of Allogeneic Stem Cell Transplantation: Case Report and Literature Review

Most cases of gas gangrene caused by Clostridium species begin with trauma-related injuries but in rare cases, spontaneous gas gangrene (SGG) can occur when patients have conditions such as advanced malignancy, diabetes, or immunosuppression. Clostridium perfringens, a rare cause of SGG, exists as normal flora of skin and intestines of human. Adequate antibiotics with surgical debridement of infected tissue is the only curative therapeutic management. Mortality rate among adults is reported range of 67-100% and majority of deaths are occurred within 24 hours of onset. We experienced a case of SGG on the trunk, buttock and thigh in a neutropenic patient with acute lymphoblastic leukemia. His clinical course was rapid and fatal during pre-engraftment neutropenic period of allogeneic stem cell transplantation.

A Case of Neurosyphilis Presenting as a Stroke in a Patient with Human Immunodeficiency Virus Infection / 대한내과학회지

While the neurologic manifestations of syphilis are diverse, stroke is a rare initial manifestation. We report a human immunodeficiency virus (HIV)-positive patient whose neurosyphilis presented as a stroke. A 42-year-old male visited the emergency room due to decreased mental functioning. Brain magnetic resonance imaging showed acute infarct on the left frontal, temporal, and parietal lobes. A serum Venereal Disease Research Laboratory (VDRL) test was positive. ELISA for HIV antibody and Western blot assays revealed he was infected with HIV. The cerebrospinal fluid (CSF) VDRL test was positive and protein was increased. The patient was treated with heparization and penicillin G for 14 days. His mental status improved with treatment, and CSF protein and VDRL titers were also decreased 3 months after treatment.

Erythropoietin Antibody-Positive Pure Red Cell Aplasia Diagnosed after Surgical Intervention for Malignant Gastric Ulcer Bleeding / 대한내과학회지

Rarely, patients on erythropoietin stimulating agent (ESA) therapy develop antibodies that neutralize both ESA and endogenous erythropoietin, resulting in antibody-mediated pure red cell aplasia (PRCA). The sudden development of severe transfusion-dependent anemia requires rapid recognition, the evaluation of PRCA, and prompt intervention after differentiating other causes of anemia, such as iron deficiency, occult bleeding, and infection. Here, we report the case of a 67-year-old male undergoing hemodialysis who presented with the anemia of chronic blood loss from a malignant gastric ulcer. Even after surgical intervention for stomach cancer and increasing the erythropoietin dosage, the anemia was not correctable and required monthly packed red blood cell transfusions. Further evaluation revealed positive erythropoietin antibody, and a bone marrow biopsy showed no red blood cell precursors, supporting the diagnosis of PRCA.

A Case of Bronchial Constriction Due to Buckwheat Allergy / 대한내과학회지

Buckwheat has been reported as a food allergen that can induce urticaria, angioedema and anaphylaxis. Moreover, it can cause occupational asthma and acute exacerbation in patients with asthma. Here, we present a case of an asthmatic patient with bronchial constriction due to buckwheat, who was treated for bronchial asthma and atopic dermatitis.

A Case of Severe Gingival Overgrowth Caused by Long-Term Amlodipine Treatment / 대한내과학회지

Amlodipine is one of the most commonly used calcium-channel blockers for the management of hypertension in Korea. Gingival overgrowth is an infrequent complication in patients receiving amlodipine treatment. A 52-year-old man on an amlodipine regimen of 10 mg/day for 25 months sought medical attention because of gradually progressive gingival enlargement. Examination of the oral cavity revealed severe gingival overgrowth. We stopped the amlodipine treatment and recommended the maintenance of good oral hygiene and a gingivectomy. Histological findings of the gingivectomy were typical of drug-induced gingival overgrowth, including epithelial thickening with proliferation, acanthosis with elongated rete ridges, and focal parakeratosis. A marked reduction in gingival overgrowth was evident 1 month after the gingivectomy and cessation of amlodipine. This report describes the case of a 52-year-old man who developed severe and histologically confirmed amlodipine-induced gingival overgrowth.

A Case of Severe Gingival Overgrowth Caused by Long-Term Amlodipine Treatment / 대한내과학회지

Amlodipine is one of the most commonly used calcium-channel blockers for the management of hypertension in Korea. Gingival overgrowth is an infrequent complication in patients receiving amlodipine treatment. A 52-year-old man on an amlodipine regimen of 10 mg/day for 25 months sought medical attention because of gradually progressive gingival enlargement. Examination of the oral cavity revealed severe gingival overgrowth. We stopped the amlodipine treatment and recommended the maintenance of good oral hygiene and a gingivectomy. Histological findings of the gingivectomy were typical of drug-induced gingival overgrowth, including epithelial thickening with proliferation, acanthosis with elongated rete ridges, and focal parakeratosis. A marked reduction in gingival overgrowth was evident 1 month after the gingivectomy and cessation of amlodipine. This report describes the case of a 52-year-old man who developed severe and histologically confirmed amlodipine-induced gingival overgrowth.

A Case of Ectopic Neurohypophysis Presenting with Hypogonadism

Pituitary stalk interruption and ectopic neurohypophysis seen on magnetic resonance Imaging (MRI) are often associated with either isolated growth hormone (GH) deficiency or combined anterior pituitary hormone deficiency, but their pathogenesis is not clear and the clinical data regarding these anatomical defect is limited. We experienced a 23-year-old male with the absence of secondary sexual characteristics and this was accompanied with pituitary stalk dysgenesis and ectopic neurohypophysis. He received growth hormone for a year when he was 12 years old due to his short stature. Sella MRI showed no visible pituitary stalk with minimal high signal change, suggesting ectopic neurohypophysis. The combined pituitary stimulation test revealed blunted responses of growth hormone, follicle stimulating hormone and luteinizing hormone. For the hypogonadotropic hypogonadism, the patient was given testosterone intramuscularly and he gradually developed secondary sexual characteristics. We concluded that the hypogonadism and growth hormone deficiency in this patient was caused by hypopituitarism due to pituitary stalk dysgenesis and ecopic nuerohypophysis.