Narrowing the Patient-Physician Gap Based on Self-Reporting and Monthly Hepatologist Feedback for Patients With Alcohol-Related Liver Disease: Interventional Pilot Study Using a Journaling Smartphone App.

BACKGROUND: Screening and intervention for alcohol use disorders (AUDs) are recommended to improve the prognosis of patients with alcohol-related liver disease (ALD). Most patients' smartphone app diaries record drinking behavior for self-monitoring. A smartphone app can be expected to also be helpful for physicians because it can provide rich patient information to hepatologists, leading to suitable feedback. We conducted this prospective pilot study to assess the use of a smartphone app as a journaling tool and as a self-report-based feedback source for patients with ALD. OBJECTIVE: The aims of this study were assessment of whether journaling (self-report) and self-report-based feedback can help patients maintain abstinence and improve liver function data. METHODS: This pilot study used a newly developed smartphone journaling app for patients, with input data that physicians can review. After patients with ALD were screened for harmful alcohol use, some were invited to use the smartphone journaling app for 8 weeks. Their self-reported alcohol intake, symptoms, and laboratory data were recorded at entry, week 4, and week 8. Biomarkers for alcohol use included gamma glutamyl transferase (GGT), percentage of carbohydrate-deficient transferrin to transferrin (%CDT), and GGT-CDT (GGT-CDT= 0.8 × ln[GGT] + 1.3 × ln[%CDT]). At each visit, their recorded data were reviewed by a hepatologist to evaluate changes in alcohol consumption and laboratory data. The relation between those outcomes and app usage was also investigated. RESULTS: Of 14 patients agreeing to participate, 10 completed an 8-week follow-up, with diary input rates between 44% and 100% of the expected days. Of the 14 patients, 2 withdrew from clinical follow-up, and 2 additional patients never used the smartphone journaling app. Using the physician's view, a treating hepatologist gave feedback via comments to patients at each visit. Mean self-reported alcohol consumption dropped from baseline (100, SD 70 g) to week 4 (13, SD 25 g; P=.002) and remained lower at week 8 (13, SD 23 g; P=.007). During the study, 5 patients reported complete abstinence. No significant changes were found in mean GGT and mean %CDT alone, but the mean GGT-CDT combination dropped significantly from entry (5.2, SD 1.2) to the week 4 visit (4.8, SD 1.1; P=.02) and at week 8 (4.8, SD 1.0; P=.01). During the study period, decreases in mean total bilirubin (3.0, SD 2.4 mg/dL to 2.4, SD 1.9 mg/dL; P=.01) and increases in mean serum albumin (3.0, SD 0.9 g/dL to 3.3, SD 0.8 g/dL; P=.009) were recorded. CONCLUSIONS: These pilot study findings revealed that a short-term intervention with a smartphone journaling app used by both patients and treatment-administering hepatologists was associated with reduced drinking and improved liver function. TRIAL REGISTRATION: UMIN CTR UMIN000045285; http://tinyurl.com/yvvk38tj.

Viral Infection in Esophageal, Gastric, and Colorectal Cancer.

The human gastrointestinal tract, which constitutes the digestive system, contains a large number of virus particles that maintain organizational homeostasis and health. Conversely, viral pathogens have also attracted attention for their involvement in the pathogenesis of certain cancers, including gastrointestinal cancers. To aid prevention and treatment of these cancers, the relevance of gastrointestinal viral factors as potential risk factors needs to be carefully investigated. This review summarizes and discusses the available literature on the relationship between the development of esophageal, gastric, and colorectal cancers and their corresponding viruses. This review reveals that research on the association between colorectal cancer and viruses, in particular, is still in its infancy compared to the association between HPV and esophageal cancer and between EBV and gastric cancer.

Gel Immersion Endoscopic Mucosal Resection (EMR) for Superficial Nonampullary Duodenal Epithelial Tumors May Reduce Procedure Time Compared with Underwater EMR (with Video).

Materials and Methods: This was a retrospective cohort study conducted in two municipal hospitals. We identified 24 patients with SNADETs of 3-18 mm in diameter who underwent UEMR or GIEMR. One lesion was excluded from the analysis because it was found to be in the stomach after surgery. The primary outcome was procedure time. Results: GIEMR significantly reduced the procedure time compared with UEMR (5 min vs. 10 min, P = 0.016). There was no significant difference between the UEMR and GIEMR groups for en bloc resection rate (93% vs. 100%, P = 1.0) and R0 resection rate (57% vs. 80%, P = 0.39). No serious complications were observed in either group. Conclusions: GIEMR of SNADET has the potential to reduce procedure time compared with UEMR and may be particularly effective in areas where immersion in water is difficult.

Efficacy of microwave ablation versus radiofrequency ablation for hepatocellular carcinoma: a propensity score analysis.

PURPOSE: To evaluate the efficacy and safety of radiofrequency ablation (RFA) and new-generation microwave ablation (MWA) for the treatment of hepatocellular carcinoma (HCC). METHODS: The propensity score matching method was applied to patients with HCC treated with MWA (93 patients) or RFA (156 patients) at a single institution from January 2014 to April 2020. The local tumor progression (LTP), intrahepatic distant recurrence (IDR), and recurrence-free survival (RFS) of the two matched therapies were analyzed using the Kaplan-Meier method. Cox proportional hazard models were used to identify risk factors for LTP and RFS. The therapeutic effects and complications of the two treatments were also compared. RESULTS: The LTP, IDR, and RFS of MWA and RFA were equivalent (LTP: hazard ratio [HR] = 0.87; 95% confidence interval [95% CI] 0.36- 2.07; P = 0.746, IDR: HR = 1.03; 95% CI 0.61-1.73; P = 0.890, RFS: HR = 1.15; 95% CI 0.69-1.91; P = 0.566). Para-vessel lesions was the only risk factor for LTP, whereas age, previous treatment, Albumin-Bilirubin score, and tumor diameter were risk factors for RFS. On the other hand, the ablation time per nodule (6.79 ± 2.73 and 9.21 ± 4.90 min; P = 0.008) and number of sessions per nodule required to achieve technical success (1.16 ± 0.39 and 1.34 ± 0.57; P = 0.009) were significantly lower in MWA than in RFA. The major complication rate of MWA and RFA was also equivalent. CONCLUSION: MWA and RFA have similar therapeutic effects and safety, although MWA has advantages over RFA regarding efficacy, including shorter ablation time and fewer sessions required.

Phospho-Smad3 signaling is predictive biomarker for hepatocellular carcinoma risk assessment in primary biliary cholangitis patients.

INTRODUCTION: Patients with primary biliary cholangitis (PBC) are at increased risk for development of hepatocellular carcinoma (HCC), particularly in the presence of comorbidities such as excessive alcohol consumption. Although liver fibrosis is an important risk factor for HCC development, earlier predictors of future HCC development in livers with little fibrosis are needed but not well defined. The transforming growth factor (TGF)-ß/Smad signaling pathway participates importantly in hepatic carcinogenesis. Phosphorylated forms (phospho-isoforms) in Smad-related pathways can transmit opposing signals: cytostatic C-terminally-phosphorylated Smad3 (pSmad3C) and carcinogenic linker-phosphorylated Smad3 (pSmad3L) signals. METHODS AND RESULTS: To assess the balance between Smad signals as a biomarker of risk, we immunohistochemically compared Smad domain-specific Smad3 phosphorylation patterns among 52 PBC patients with various stages of fibrosis and 25 non-PBC patients with chronic hepatitis C virus infection. HCC developed in 7 of 11 PBC patients showing high pSmad3L immunoreactivity, but in only 2 of 41 PBC patients with low pSmad3L. In contrast, 9 of 20 PBC patients with minimal Smad3C phosphorylation developed HCC, while HCC did not occur during follow-up in 32 patients who retained hepatic tumor-suppressive pSmad3C. Further, PBC patients whose liver specimens showed high pSmad3L positivity were relatively likely to develop HCC even when little fibrosis was evident. CONCLUSION: In this study, Smad phospho-isoform status showed promise as a biomarker predicting likelihood of HCC occurrence in PBC. Eventually, therapies to shift favorably Smad phospho-isoforms might decrease likelihood of PBC-related HCC.

Short term treatment results of local ablation with water-cooled microwave antenna for liver cancer: Comparison with radiofrequency ablation.

The aim of the present study was to evaluate the efficacy and safety of the new-generation percutaneous microwave ablation (MWA) compared with the radiofrequency ablation (RFA) system for the treatment of hepatocellular carcinoma (HCC). A retrospective study was conducted from January 2014 to February 2019. A total of 44 patients and 52 nodules (mean tumor size, 17.2±4.9 mm) were treated with MWA, and 55 patients and 70 nodules (mean tumor size, 17.7±6.4 mm) were treated with RFA. After 4 days of treatment, the direct effects of ablation were assessed using dynamic CT, and after discharge, a follow-up dynamic CT scan was performed every 3-4 months. Treatment efficacy, complications and local recurrence were recorded. For MWA and RFA, the average number of CT sessions were 1.05±0.23 and 1.28±0.54, respectively, and the mean ablation times were 5.0±2.0 and 8.1±4.8 min. Following MWA and RFA, the ablation ranges that were evaluated with the axial images were 31.9±5.5 and 33.3±9.0 mm, respectively, in the long-axis diameter and 27.6±5.3 and 23.4±6.8 mm, respectively, in the short-axis diameter. The flatness ratios of the ablation regions were 0.13±0.09 and 0.29±0.14 (axial image) and 0.11±0.07 and 0.28±0.14 (coronal image), respectively. The rates of complete tumor necrosis were comparable. The complication rates were 13.6% (MWA) and 14.5% (RFA), which were not significantly different. The cumulative local recurrence rates were not significantly different between the two methods (one-year recurrence rate, MWA: 6.91%, RFA: 5.17%). MWA was therefore indicated to be an effective treatment for HCC in respect to session number, treatment time and spherical ablation.

Smad Phospho-Isoforms for Hepatocellular Carcinoma Risk Assessment in Patients with Nonalcoholic Steatohepatitis.

Nonalcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) sometimes occurs in mildly fibrotic livers, while HCC incidence in NASH-related cirrhosis is lower than and less predictable than in hepatitis C virus (HCV)-related cirrhosis. Transforming growth factor (TGF)-ß signaling in hepatocytic nuclei is implicated in fibrosis and carcinogenesis. TGF-ßtype I receptor (TßRI) and c-Jun N-terminal kinase (JNK) differentially phosphorylate the mediator Smad3, resulting in 2 distinct phospho-isoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). In mature hepatocytes, oncogenic signaling via the JNK/pSmad3L pathway antagonizes signaling via the tumor-suppressive TßRI/pSmad3C pathway. We immunohistochemically examined domain-specific Smad3 phosphorylation in liver biopsy specimens from 30 NASH patients representing different fibrotic stages and 20 chronically infected hepatitis C patients as controls, correlating Smad3 phosphorylation with clinical course. HCC occurred during follow-up in 11 of 12 NASH patients with abundant pSmad3L and limited pSmad3C but in only 2 of 18 with limited pSmad3L. In contrast, HCC developed in 12 of 15 NASH patients with limited pSmad3C but only 1 of 15 with abundant pSmad3C. Two of fourteen NASH patients with mild fibrosis developed HCC, their hepatocytic nuclei showed abundant pSmad3L and limited pSmad3C. Five of sixteen patients with severe fibrosis did not develop HCC, their hepatocytic nuclei showed limited pSmad3L and abundant pSmad3C. Smad phospho-isoforms may represent important biomarkers predicting HCC in NASH and potential therapeutic targets for preventing NASH-related HCC.

Acute necrotizing pancreatitis as a fatal complication following DC Bead transcatheter arterial chemoembolization for hepatocellular carcinoma: A case report and review of the literature.

Transcatheter arterial chemoembolization (TACE) is one of the most effective palliative measures for patients with inoperable hepatocellular carcinoma (HCC). Acute pancreatitis is a rare but well-known complication following TACE. We herein present the case of a patient with HCC who developed fatal complications (acute necrotizing pancreatitis and upper gastrointestinal ulcers) after TACE with DC Beads. The patient was diagnosed with HCC in segments 4 and 8, measuring ~70 mm in greatest diameter, and he was treated by TACE. Hepatic arteriography revealed replacement of the origin of the right hepatic artery to the superior mesenteric artery, while the left hepatic artery originated from the celiac artery. After selection of the segmental arterial branches feeding the tumor, 2 ml of 100-300-µm-sized DC Beads loaded with 150 mg epirubicin were injected through the microcatheter. The patient complained of abdominal pain after the TACE procedure. Upper gastrointestinal endoscopy revealed longitudinal ulcers from the esophagus to the duodenum, and contrast-enhanced computed tomography revealed swelling of the pancreas and focal areas of low density in the pancreatic body, suggesting necrosis. The patient developed respiratory insufficiency, renal failure and sepsis, and finally succumbed to the complications 54 days after the procedure, despite general management of the acute pancreatitis. An autopsy revealed that the main cause of the patient's death was extensive pancreatic necrosis due to a gastroduodenal artery embolism after TACE with DC Beads. Therefore, it is crucial for treating physicians to be aware of this complication following TACE with DC Beads, particularly in patients with anatomical variations.

The Prevalence and Implication of Zinc Deficiency in Patients With Chronic Liver Disease.

BACKGROUND: Patients with liver cirrhosis often exhibit zinc deficiency. Although zinc is involved in many bioactivities, many aspects of clinical implications of zinc deficiency in liver cirrhosis remain unclear. We aimed to reveal the prevalence and implications of zinc deficiency in liver cirrhosis by assessing associations with parameters such as clinical symptoms and laboratory data. METHODS: In 235 cirrhosis patients enrolled at multiple medical institutions in 2009, we assessed how blood zinc levels were associated with their clinical symptoms, patients characteristics, and liver function test results. RESULTS: Blood zinc levels were most strongly correlated with blood albumin levels among the study parameters (r = 0.587, P < 0.0001). When blood albumin levels were ≤ 3.5 g/dL, blood zinc levels were < 70 µg/dL in 88% of patients. Additionally, significant correlations were observed with age (r = -0.253, P = 0.0014), aspartate aminotransferase levels (r = -0.254, P = 0.0020), total bilirubin levels (r = -0.222, P = 0.0053), prothrombin time (r = -0.255, P = 0.0029), branched-chain amino acid to tyrosine ratio (r = 0.357, P < 0.0001), Child-Pugh score (r = 0.469, P < 0.0001), ammonia levels (r = -0.246, P = 0.0028), and total cholesterol levels (r = 0.314, P < 0.0001). Blood zinc levels were significantly lower in patients with edema/ascites (P < 0.0001), those with hepatic encephalopathy (P = 0.0215), those receiving oral diuretics (P = 0.0045), and those receiving oral branched-chain amino acids (P < 0.0001) than in those without these conditions. CONCLUSIONS: Zinc deficiency is prevalent in cirrhosis patients, whereas nitrogen metabolic disorders, particularly hypoalbuminemia, can be an indicator of zinc deficiency. Thus, cirrhosis patients exhibiting a nitrogen metabolic disorder should be examined for the presence of zinc deficiency.

S-1 monotherapy in a patient with cholangiolocellular carcinoma: A case report.

A 71-year-old man with alcoholic cirrhosis was found to have multiple hypervascular lesions in the liver on enhanced computed tomography. An ultrasound-guided biopsy of the lesion was performed. Immunohistochemical analysis for hepatocyte paraffin 1 expression was negative; cytokeratin (CK) 7, CK19, epithelial cell adhesion molecule and epithelial membrane antigens were positive; mucicarmine staining was negative. The tumor was thus histologically diagnosed as cholangiolocellular carcinoma (CoCC). The tumor was inoperable due to the associated advanced liver disease. In addition, the patient preferred systemic chemotherapy using only orally administered agents. Thus, S-1 monotherapy was recommended. S-1 was initially administered orally at a dose of 80 mg/day. Although the levels of tumor marker (prothrombin induced by vitamin K absence/antagonist-II and carbohydrate antigen 19-9) levels were marginally elevated, their values did not change over the entire course. The patient achieved a partial response according to the Response Evaluation Criteria In Solid Tumors (RECIST) and modified RECIST 1 year after chemotherapy initiation. In conclusion, S-1 monotherapy exhibited promising efficacy against unresectable CoCC.

Non-rigid image registration with anatomical structure constraint for assessing locoregional therapy of hepatocellular carcinoma.

PURPOSE: Assessing the treated region with locoregional therapy (LT) provides valuable information for predicting hepatocellular carcinoma (HCC) recurrence. The commonly used of assessment method is inefficient because it only compares two-dimensional CT images manually. In our previous work, we automatically aligned the two CT volumes to evaluate the therapeutic efficiency using registration algorithms. The non-rigid registration is applied to capture local deformation, however, it usually destroys internal structure. Taking these into consideration, this paper proposes a novel non-rigid registration approach for evaluating LT of HCC to maintain the image integrity. METHOD: In our registration algorithm, a global affine transformation combined with localized cubic B-spline is used to estimate the significant non-rigid motions of two livers. The proposed method extends a classical non-rigid registration based on mutual information (MI) that uses an anatomical structure term to constrain the local deformation. The energy function can be defined based on the total one associated with the anatomical structure and deformation information. Optimal transformation is obtained by finding the equilibrium state in which the total energy is minimized, indicating that the anatomical landmarks have found their correspondences. Thus, we can use the same transformation to automatically transform the ablative region to the optimal position. RESULTS: Registration accuracy is evaluated using the clinical data. Improved results are obtained with respect to all criteria in our proposed method (MI-LC) than those in the MI-based non-rigid registration. The landmark distance error (LDE) of MI-LC is decreased by an average of 3.93mm compared to the case of MI-based registration. Moreover, it could be found regardless of how many landmarks applied in our proposed method, a significant reduction in LDE values using registrations based on MI-LC compared with those based on MI is confirmed. CONCLUSION: Our proposed approach can guarantee the continuity, the accuracy and the smoothness of structures by constraining the anatomical features. The results clearly indicate that our method can retain the local deformation of the image. In addition, it assures the anatomical structure stability.

Interstitial pneumonia induced by sorafenib in a patient with hepatocellular carcinoma: An autopsy case report.

Sorafenib is a multikinase inhibitor currently approved in Japan for the treatment of unresectable hepatocellular carcinoma. Interstitial pneumonia induced by sorafenib may have a fatal outcome, and therefore, has recently been the focus of many studies. The current report presents an autopsy case of diffuse alveolar damage (DAD) that occurred in a 59-year-old male, who had been treated with sorafenib. The patient had been given sorafenib for six months and had exhibited no respiratory symptoms during this time. However, 19 days after sorafenib treatment was resumed, acute interstitial pneumonia developed. In previously reported cases, the first symptoms of pulmonary toxicity appeared following a limited treatment duration with sorafenib; this was in contrast to the patient in the current study, who developed the first symptoms after eight months. We therefore conclude that physicians must be aware of interstitial pneumonia as a potential pulmonary toxicity associated with sorafenib treatment when treatment with sorafenib is resumed, even after prolonged use. In addition, to best of our knowledge, this is the first case of a postmortem examination reported in patient with interstitial pneumonia induced by sorafenib treatment.

Severe acute hepatitis in a printing company worker: a case study.

OBJECTIVES: It has been reported that chlorinated organic solvent is a cause of hepatitis. METHODS: we investigate clinical and pathological findings of a patient with severe acute hepatitis who was exposed to chlorinated organic solvents. RESULTS: A 34-year-old man who was exposed to chlorinated organic solvents including dichloromethane, 1,2-dichloropropane, and trichloroethylene, presented with general fatigue, vomiting, and diarrhea. At admission, his laboratory test results showed extremely elevated aspartate aminotransferase (4,872 IU/l), alanine aminotransferase (3,000 IU/l), and lactate dehydrogenase (11,600 IU/l) levels and a prothrombin level below normal (41%). No encephalopathy was noted. These findings were indicative of severe acute hepatitis. Viral hepatitis, autoimmune hepatitis, alcoholic disease, bile duct disease, and viral infection were excluded as causes of hepatitis by clinical, laboratory, and imaging findings. After diagnosis, the patient was administered fresh frozen plasma and glucagon-insulin therapy. Liver function recovered within a few weeks, and a liver biopsy performed 25 days after admission showed the recovery phase after acute liver damage. CONCLUSIONS: These clinical and pathological findings indicate that exposure to chlorinated organic solvents may have induced severe acute hepatitis in this patient.