Lysyl oxidase-like 2 as a predictor of hepatocellular carcinoma in patients with hepatitis C virus after sustained virological response.

Lysyl oxidase-like 2 (LOXL2) mediates the crosslinking of extracellular collagen, reflecting qualitative changes in liver fibrosis. This study aimed to validate the utility of serum LOXL2 levels as a predictive biomarker for the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection who achieved a sustained virological response (SVR). This retrospective study included 137 patients with chronic HCV infection without history of HCC development and who achieved SVR via direct-acting antiviral therapy. Median LOXL2 levels decreased significantly after SVR achievement (pre-Tx, 2.33 ng/mL; post-Tx, 1.31 ng/mL, p < 0.001). Post-Tx LOXL2 levels, fibrosis-4 index, platelet counts, Wisteria floribunda agglutinin-positive human Mac-2 binding protein levels, and alpha-fetoprotein (AFP) levels were identified as independent predictive factors for post-SVR HCC development in the univariate analysis. The incidence of post-SVR HCC development was significantly higher in patients with post-Tx LOXL2 levels ≥ 2.08 ng/mL and AFP levels ≥ 5.0 ng/mL than in patients with elevated levels of either marker or with lower marker levels. Serum LOXL2 levels can serve as a predictive biomarker for HCC development after achieving SVR. The combination of serum LOXL2 and AFP levels provides robust risk stratification for HCC development after SVR, suggesting an enhanced surveillance strategy.

Mac-2-binding protein glycan isomer predicts all malignancies after sustained virological response in chronic hepatitis C.

Despite reports of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection after achieving sustained virological response (SVR), only few studies have demonstrated the incidence of other (non-HCC) malignancies. This study aimed to clarify the incidence, survival probability, and factors associated with malignancy, especially non-HCC malignancies, in patients with chronic HCV infection after achieving SVR. In this retrospective study, records of 3580 patients with chronic HCV infection who achieved SVR following direct-acting antiviral (DAA) treatment were analyzed. The cumulative post-SVR incidence of non-HCC malignancies was 0.9%, 3.1%, and 6.8% at 1, 3, and 5 years, respectively. The survival probability for patients with non-HCC malignancies was 99.1%, 78.8%, and 60.2% at 1, 3, and 5 years, respectively, and the rate was significantly lower than that for patients with HCC. The Cox proportional hazards regression model identified Mac-2-binding protein glycan isomer (M2BPGi) cutoff index (COI) ≥ 1.90 at baseline and ≥ 1.50 at 12 weeks following DAA treatment as significant and independent factors associated with the post-SVR incidence of non-HCC malignancies. Furthermore, patients with either M2BPGi COI ≥ 1.90 at baseline or M2BPGi COI ≥ 1.50 at SVR12 had a significantly higher risk of post-SVR incidence of non-HCC malignancies than of HCC. Conclusion: M2BPGi measurements at baseline and SVR12 may help predict the post-SVR incidence of non-HCC malignancies in patients with chronic HCV infection who achieved SVR following DAA treatment. Early identification of these patients is critical to prolong patient survival.

Retrospective multicentre study on the effectiveness of first-line direct-acting antivirals against hepatitis C virus genotype-1.

WHAT IS KNOWN AND OBJECTIVE: In Japan, ledipasvir/sofosbuvir, elbasvir/grazoprevir and glecaprevir/pibrentasvir are recommended as first-line treatments for patients with untreated hepatitis C virus genotype 1. Although they have demonstrated a high efficacy in clinical trials, there are no direct comparative studies. Clarification of their effectiveness and safety in real-world clinical practice is required. Therefore, we conducted a retrospective multicentre study on the effectiveness of these direct-acting antivirals in real-world clinical practice. METHODS: We retrospectively evaluated the clinical data of untreated patients with persistent HCV genotype 1 infection who started first-line treatment with ledipasvir/sofosbuvir, elbasvir/grazoprevir or glecaprevir/pibrentasvir between September 2015 and January 2019 at 11 medical institutions in Japan. The primary efficacy endpoint was a sustained virologic response after 12 weeks of treatment. The secondary endpoints included sustained virologic response after 24 weeks of treatment and end of treatment response. The safety endpoint was treatment completion rate. RESULTS AND DISCUSSION: During the study, 420 patients (median age, 70 years; 181 males) received ledipasvir/sofosbuvir, 48 (median age 72, years; 29 males) received elbasvir/grazoprevir and 63 (median age 66, years; 35 males) received glecaprevir/pibrentasvir. For ledipasvir/sofosbuvir, elbasvir/grazoprevir and glecaprevir/pibrentasvir, the sustained virologic response after 12 weeks of treatment was 98.6%, 97.9% and 100%; the sustained virologic response after 24 weeks of treatment was 99.0%, 97.7% and 100%; the end of treatment response was 99.8%, 97.9% and 98.4%; and the treatment completion rate was 98.3%, 91.7% and 100% respectively. WHAT IS NEW AND CONCLUSION: In real-world clinical practice, hepatitis C virus treatment with ledipasvir/sofosbuvir, elbasvir/grazoprevir and glecaprevir/pibrentasvir was effective with safety.

Long-term pegylated interferon monotherapy following 72 weeks of pegylated interferon and ribavirin in hepatitis C virus genotype-1-infected slow responders.

OBJECTIVE: Slow responders to pegylated interferon (Peg-IFN) and ribavirin (RBV) among patients infected with hepatitis C virus (HCV) genotype 1 may benefit from an extended treatment course. The aim of this study was to determine the efficacy of persistent negative serum HCV RNA over 96 weeks during long-term Peg-IFN monotherapy following 72 weeks of combination therapy. METHODS: A total of 46 HCV genotype 1-infected slow responders were treated for 72 weeks with Peg-IFN and RBV combination therapy alone (n=25) or additional long-term biweekly treatment with 90 µg of Peg-IFN-α2a (n=21). The criterion for the completion of long-term Peg-IFN monotherapy was defined as the attainment of constantly negative HCV RNA in the serum over 96 weeks during IFN treatment. RESULTS: The patients with sustained negative serum HCV RNA during 96 weeks of IFN treatment had a higher rate of sustained virological response (SVR) than those without (81 vs. 40%, p=0.012). A multivariate analysis identified sustained negativity of serum HCV RNA over 96 weeks of IFN treatment to be a predictive factor for SVR. CONCLUSION: In the present study, sustained negative serum HCV RNA over 96 weeks during long-term Peg-IFN monotherapy following 72 weeks of combination therapy of Peg-IFN and RBV resulted in beneficial virological outcomes among HCV genotype 1-infected slow responders.

[A case of hemorrhage from varices of an interposed jejunum after choledochojejunostomy treated successfully by endoscopic injection using α-cyanoacrylate monomer].

A 73-year-old woman was admitted with gastrointestinal bleeding. She had undergone pylorus-preserving pancreaticoduodenectomy, hepaticojejunostomy and pancreatojejunostomy for pancreatic cancer a year earlier. Gastrointestinal endoscopy revealed bleeding from varices in an interposed jejunum. Enhanced CT showed an extrahepatic portal venous obstruction and cavernous transformation of the portal vein, which were complications of these operations. We performed endoscopic injection using α-cyanoacrylate monomer for the varices. After 4 treatments, the bleeding stopped. We concluded that endoscopic injection using α-cyanoacrylate monomer was effective and useful treatment for bleeding from hepatopetal varices, including cavernous transformation of the portal vein. This method is also useful in emergency situations.

[A case of jejunal perforation in gallstone ileus].

Gallstone ileus is a rare but important cause of small bowel obstruction in the geriatric population. A 65-year-old man with a twenty year history of cholecystolithiasis was admitted to our hospital with abdominal pain and vomiting. Physical exams showed abdominal defence and rebound tenderness. A plain abdominal X-ray suggested a small bowel obstruction and pneumobilia. CT scan revealed a 2.5-cm gallstone at the jejunum and air in the biliary tree. The patient underwent a emergency laparotomy based on a diagnosis of panperitonitis with a perforation associated with gallstone ileus. Operative findings revealed a jejunal perforation and a impacted stone on the anal side of perforation. Enterolithotomy and jejunal resection were performed with cholecystectomy and repairment of the cholecystoduodenal fistula.

Carcinosarcoma of the liver with mesenchymal differentiation.

We report an extremely rare case where a mesenchymal differentiation, especially embryonal sarcoma, was demonstrated in cholangiocarcinoma. At autopsy, a yellowish-white tumor (15 cm x 12 cm) was found in the right hepatic lobe, and there were several daughter nodules in both hepatic lobes. Histologically, most of the main tumor and all of the daughter nodules examined showed sarcomatous changes (spindle cells, pleomorphic cells and hyalization). Histologic examination of a part of the main tumor disclosed a focus of adenocarcinoma within the tumor. The frequent transitions between the adenocarcinomatous areas and the sarcomatous areas suggested that sarcomatous transformation occurred in the cholangiocarcinoma and then spread rapidly. Immunohistochemically, the adenocarcinomatous elements were positive for cytokeratin, carcinoembryonic antigen (CEA) and epithelial membrane antigen, and negative in the sarcomatous cells. Vimentin was positive only in the sarcomatous elements. The findings of the present case support the view that carcinosarcomas represent carcinomas that develop sarcomatous elements via metaplasia of the epithelial element.