Time-course changes in liver functional reserve after successful sofosbuvir/velpatasvir treatment in patients with decompensated cirrhosis.

AIM: Direct-acting antivirals (DAAs) are currently available even for patients with decompensated cirrhosis. Reportedly, hepatic functional reserve improved in the short term after achievement of sustained virologic response (SVR). We aimed to clarify the outcomes after achievement of SVR in patients with decompensated cirrhosis who were treated by DAAs in real-world clinical practice. METHODS: A prospective, multicenter study of 12-week sofosbuvir/velpatasvir was conducted in 86 patients with decompensated cirrhosis, who were evaluated for 48 weeks post-treatment. RESULTS: The cohort included 8 patients with Child-Pugh class A, 56 with B, and 22 with C. The proportion of Child-Pugh class A patients increased from 9.1% at baseline to 44.1% at 48 weeks post-treatment, while that of class B and C patients decreased from 66.2% to 35.1% and from 24.7% to 14.3%, respectively. Among the patients with Child-Pugh class B and C, univariate analysis identified low total bilirubin, Child-Pugh score, Child-Pugh class B, ALBI score, and high serum albumin as factors associated with improvement to Child-Pugh class A. The optimal cut-off value of the factors for predicting improvement to Child-Pugh class A were 1.4 mg/dl for total bilirubin, 2.9 g/dl for serum albumin, 8 points for Child-Pugh score, and -1.88 for ALBI score. CONCLUSION: Achievement of SVR with sofosbuvir/velpatasvir improved the liver functional reserve at 12 weeks post-treatment and maintained the stable effects until 48 weeks post-treatment in patients with decompensated cirrhosis. Specifically, the patients with less advanced conditions had the likelihood of improving to Child-Pugh class A at 48 weeks post-treatment.

Real-world experience of 12-week direct-acting antiviral regimen of glecaprevir and pibrentasvir in patients with chronic hepatitis C virus infection.

BACKGROUND: In clinical trials, a pangenotype direct-acting antiviral (DAA) regimen consisting of glecaprevir (GLE) and pibrentasvir (PIB) exhibited high virologic efficacy and tolerability in patients with hepatitis C virus (HCV) infection. This study sought to confirm these findings in real-world settings, focusing on patients with cirrhosis, history of DAA failure, or HCV genotype 3 who were treated with a 12-week regimen in a large multicenter study from Japan. METHODS: In a nationwide multicenter prospective cohort study, we analyzed background characteristics, tolerability, and treatment outcome of patients who underwent a 12-week GLE/PIB regimen. RESULTS: Of 1190 patients, 509 (42.8%) underwent the 12-week regimen, and the remaining patients underwent an 8-week regimen. The rate of sustained virologic response (SVR) of patients treated with the 12-week regimen was 99.0%, comparable with that of patients treated with the 8-week regimen. The adverse events were observed in 29.1% of patients. The main adverse event was pruritus, which was observed in 14.7%. Ten patients (2.0%) discontinued therapy during treatment period. CONCLUSION: The 12-week GLE/PIB regimen was well-tolerated with high virologic efficacy in patients with cirrhosis, experience of DAA, or HCV genotype 3; tolerability and SVR rate were comparable with those of DAA-naïve, non-cirrhotic, non-genotype 3 patients who underwent 8-week regimen.

Marked heterogeneity in the diagnosis of compensated cirrhosis of patients with chronic hepatitis C virus infection in a real-world setting: A large, multicenter study from Japan.

BACKGROUND AND AIM: The presence of cirrhosis is an important factor for the management of patients with hepatitis C virus (HCV) infection and it determines the duration of treatment for HCV with the direct-acting antiviral (DAA) regimen of glecaprevir (GLE) and pibrentasvir (PIB), that is, 8 or 12 weeks, if patients do not have a history of DAA failure. However, in real-world settings, determination of cirrhosis depends on the discretion of the attending hepatologists, and it is unclear whether compensated cirrhosis was homogenously diagnosed or not. In this study, we investigated the real-world diagnosis of cirrhosis by characterizing DAA-naïve patients who underwent a 12-week GLE/PIB regimen in whom cirrhosis was diagnosed, comparing their characteristics with those of patients who underwent an 8-week regimen in whom cirrhosis was absent. METHODS: In a large, multicenter cohort study, we compared background characteristics and treatment outcomes among DAA-naïve patients who underwent an 8-week versus a 12-week GLE/PIB regimen. RESULTS: Among 977 patients enrolled, 296 (30.3%) were determined to have cirrhosis and underwent a 12-week regimen. Some patient characteristics largely overlapped between the two groups, including liver fibrosis indices. Sustained viral response rates were similar between groups after adjusting liver fibrosis index with propensity score matching. CONCLUSION: Although adequately diagnosed, the determination of cirrhosis varied widely among institutions or by hepatologists in real-world settings, and the severity of liver fibrosis overlapped significantly between patients in whom compensated cirrhosis was determined to be present and patients in whom cirrhosis was absent. Virologic efficacy was similar after adjusting for the degree of liver fibrosis.

Evaluation of 8-week glecaprevir/pibrentasvir treatment in direct-acting antiviral-naïve noncirrhotic HCV genotype 1 and 2infected patients in a real-world setting in Japan.

Based on high efficacy and safety demonstrated in clinical trials, treatment with glecaprevir/pibrentasvir (G/P) for 8 weeks is recommended for hepatitis C virus (HCV)-infected patients who are direct-acting antiviral (DAA) naïve, genotype 1 or 2, and noncirrhotic. The aim of this study was to validate real-world experience with 8-week G/P treatment in Japan. We conducted a prospective observational cohort study in 554 patients who underwent 8-week treatment from among 1,022 patients who initiated G/P therapy. The majority (54.5%) were male, with a median age of 66 years, and HCV genotype distribution was genotype 1, 43.8%; genotype 2, 55.3%; and mixed subtype, 0.9%. Overall, the sustained virologic response rate at 12 weeks (SVR12) was 92.8% (530/571) in the intention-to-treat population and 99.3% (526/530) in the per-protocol population. The SVR12 rates by subgroups were as follows: subtype 1a, 100% (6/6); 1b, 100% (189/189); 2a, 99.3% (150/151); 2b, 99.0% (103/104); and mixed subtype, 50% (2/4). Among four patients with virologic failure following 8-week treatment with G/P, none had baseline polymorphisms or treatment-emergent amino acid substitutions in NS3. However, 2 of 4 patients with virologic failure had treatment-emergent amino acid substitutions in NS5A. Adverse events (AEs) were reported in 21.5% of patients and 1.2% of patients discontinued due to drug-related AEs. In conclusion, G/P treatment for 8 weeks was safe and effective for DAA-naïve noncirrhotic genotype 1 or 2 patients in a real-world clinical setting in Japan.

Liver stiffness reduction correlates with histological characteristics of hepatitis C patients with sustained virological response.

BACKGROUND & AIMS: We investigated the correlation between histological characteristics and changes in liver stiffness (LS) in patients with sustained virological response (SVR) using acoustic radiation force impulse (ARFI) elastography. METHODS: In this prospective study, we enrolled 176 hepatitis C patients with SVR who underwent ARFI elastography and liver biopsy before antiviral treatment, and serial ARFI elastography at the end of treatment (EOT) and at 24 weeks after the EOT. To compare the long-term changes in LS in patients with SVR using ARFI elastography, another group of 140 patients who had undergone paired biopsy after achieving SVR was included. RESULTS: Mean LS values were 1.60±0.63 m/s, 1.48±0.56 m/s and 1.37±0.62 m/s at baseline, EOT and 24 weeks after EOT, respectively, P<.001. Higher inflammatory activity at baseline was associated with an improvement in LS at the EOT, with an odds ratio of 1.940. Significant fibrosis at baseline was associated with an improvement in LS at 24 weeks after the EOT, with an odds ratio of 2.617. Among patients in the paired biopsy group with baseline fibrosis stage identical to the ARFI group, LS values at 24 weeks after the EOT did not show any difference with values at 5 years after EOT. CONCLUSIONS: Pre-treatment histological characteristics influence LS reduction after SVR is achieved.

Impact of myosteatosis on skeletal muscle volume loss in patients with chronic liver disease.

BACKGROUND AND AIM: Severe muscle volume loss is a recognized negative prognostic factor in patients with chronic liver disease. However, the effect of skeletal muscle fat deposition, referred to as myosteatosis on muscle volume loss remains unclear. The aim of this study was to investigate the relationships between myosteatosis and skeletal muscle volume loss. METHODS: We enrolled 362 patients with chronic liver disease (186 men, 176 women; mean age 68.4 ± 10.0 years, 94 with cirrhosis) who underwent liver biopsy and computed tomography scanning between January 2013 and February 2017. A transverse computed tomography image of each scan at the third lumbar vertebra was used to evaluate skeletal muscle tissues. RESULTS: Prevalence of skeletal muscle volume loss and myosteatosis were 36% and 82%, respectively. Of those with skeletal muscle volume loss, 93% have concomitant myosteatosis. Univariate analysis revealed that higher age, female, lower body mass index (BMI), higher serum albumin, lower alanine aminotransferase (ALT), lower gamma-glutamyl transpeptidase, lower total bilirubin, lower α-fetoprotein, lower skeletal muscle attenuation, and liver steatosis were significantly associated with skeletal muscle volume loss. Multivariate logistic regression analysis confirmed that lower BMI (odds ratio [OR] 5.26, 95% confidence interval [CI], 3.21-8.54; P < 0.001), presence of myosteatosis (OR, 2.82; 95% CI, 1.26-6.30; P < 0.001), lower ALT (OR, 2.04; 95% CI, 1.18-3.52; P = 0.010), and female (OR, 1.71; 95% CI, 1.04-2.28; P = 0.034) were significant independent factors associated with skeletal volume loss. CONCLUSIONS: Myosteatosis, low BMI, low ALT, and female are associated with skeletal muscle volume loss in patients with chronic liver disease.

Comparison of direct sequencing and Invader assay for Y93H mutation and response to interferon-free therapy in hepatitis C virus genotype 1b.

BACKGROUND AND AIM: Virologic failure of interferon-free therapy has been associated with Y93H mutation in the non-structure 5A region in hepatitis C virus (HCV) genotype 1b, and screening is recommended. A simple assay based on Q-Invader technology was developed for Y93H mutant screening to reduce cost and effort. The present study sought to compare two methods of detection of Y93H mutation and to evaluate the effect of Y93H mutation on response to interferon-free therapy. METHODS: Y93H mutation was examined in 258 patients with HCV genotype 1b using both direct sequencing analysis and the polymerase chain reaction (PCR)-Invader assay. Daclatasvir and asunaprevir or ledipasvir and sofosbuvir therapy was administered to 205 patients whose sustained virological responses (SVR) were checked. RESULTS: Hepatitis C virus was detected in 232 of 258 patients by direct sequencing and in 236 of 258 patients by the PCR-Invader assay. Forty of 231 cases were defined as Y93 mutation by direct sequencing, and 46 of 236 cases were defined as Y93 mutation by the PCR-Invader assay. SVR of patients who were Y93H by direct sequencing, Y93H by the PCR-Invader assay, and Y93H by both methods was 62.5%, 82.4%, and 50%, respectively. CONCLUSIONS: The sensitivity of the PCR-Invader assay was similar to that of direct sequencing analysis; however, the PCR-Invader assay had a better ability to detect minor strains. Combination of the two assays would improve prediction of the response to daclatasvir and asunaprevir, but Y93H mutation had little effect on SVR in ledipasvir and sofosbuvir therapy.

Efficacy and tolerability of an IFN-free regimen with DCV/ASV for elderly patients infected with HCV genotype 1B.

BACKGROUND & AIMS: Anti-hepatitis C virus (HCV) therapy by interferon (IFN)-free regimen with oral direct-acting antiviral drugs are tolerable in aged patients, with fewer adverse effects than IFN-based therapies. We investigated the efficacy and tolerability of an IFN-free anti-HCV therapy in extremely aged patients, as well as the survival benefit of sustained virologic response (SVR). METHODS: Following IFN-free therapy with daclatasvir and asunaprevir, tolerability and SVR rate were compared between 115 HCV genotype 1-infected patients aged 80years or older, 151 patients in their 70s (⩾70 and <80years), and 115 patients under the age of 70. One-year mortality and morbidity in patients aged ⩾80years were compared between SVR patients and propensity score-matched patients with persistent HCV infection. RESULTS: The SVR rate was 96.5% in patients ⩾80years, comparable to that in patients aged ⩾70 and <80years (95.4%) and patients aged <70years (93.9%). There were no differences in treatment discontinuation rate (2.6%, 1.3%, and 0.9%, respectively). One-year mortality was significantly lower in SVR patients (2.7%) than in patients with persistent HCV infection (15.3%, p=0.0016). Whereas 1-year mortality due to liver-related diseases was 8.1% in patients with persistent HCV infection who were aged ⩾80years, no SVR patients died from liver diseases within 1-year after the end of therapy. CONCLUSIONS: IFN-free therapy for HCV infection was associated with high tolerability and antiviral efficacy, even in patients aged ⩾80years. In addition, there seemed to be a survival benefit from the eradication of HCV in this population. LAY SUMMARY: IFN-free therapy with oral direct-acting antiviral drugs (daclatasvir and asunaprevir) for HCV infection showed similar tolerability and antiviral efficacy in patients aged ⩾80years as in younger patients (patients aged ⩾70 and <80years and patients aged <70years), with an SVR rate over 90% and no severe adverse effects. There was a survival benefit from the eradication of HCV even in patients aged ⩾80years.

Characteristics and prognosis of hepatocellular carcinoma detected in patients with chronic hepatitis C after the eradication of hepatitis C virus: A multicenter study from Japan.

AIM: We investigated the characteristics and prognosis of patients with hepatocellular carcinoma (HCC) diagnosed after sustained virological response (SVR) to antiviral therapy for chronic hepatitis C virus (HCV) infection, namely, the eradication of HCV, according to surveillance status after SVR. METHODS: In this multicenter study, liver function at HCC diagnosis and progression of HCC among patients with HCC diagnosed after SVR were compared. Outcomes were also investigated. RESULTS: In patients not under surveillance after SVR, HCC was significantly more advanced at diagnosis, with tumors that were larger in size and of higher stage than in patients who continued under surveillance after SVR. Survival rates were significantly lower in patients not under surveillance (P < 0.0001). Among patients who were under surveillance, those with a 6-month surveillance interval had larger and higher stage HCC than patients with a 3-month interval. Recurrence rates in patients with a 6-month surveillance interval were significantly higher than in patients with a 3-month surveillance interval (P = 0.0417). CONCLUSION: Lack of surveillance after SVR was obviously associated with more advanced HCC at detection, resulting in poor prognosis. More importantly, there may be a difference in the severity of HCC at diagnosis and prognosis based on the surveillance interval after SVR. Establishing guidelines how to survey patients with chronic hepatitis C after SVR is necessary.

α-fetoprotein levels after interferon therapy predict regression of liver fibrosis in patients with sustained virological response.

BACKGROUND AND AIMS: Eradicating chronic hepatitis C virus (HCV) infection improves liver fibrosis and reduces hepatocellular carcinoma (HCC) incidence in chronic HCV patients. We evaluated the relationship between fibrosis regression, as assessed by sequential biopsies, and clinical factors of patients with sustained virological response (SVR). METHODS: We retrospectively enrolled 130 patients (74 men; 60.1 ± 8.1 years) with chronic HCV treated with interferon and ribavirin therapy who achieved SVR. To evaluate the change in fibrosis stage over time, all patients underwent a pre-therapy initial biopsy and a second biopsy after achieving SVR. RESULTS: The mean time between biopsies was 5.5 ± 1.2 years. Fibrosis stage regressed in 55 patients (42.3%), remained stable in 69 (53.1%), and progressed in 6 (4.6%). The mean fibrosis stage significantly decreased, from 2.01 ± 0.99 units to 1.61 ± 1.24 units (P < 0.001). Aspartate aminotransferase, γ-glutamyltransferase, and α-fetoprotein (AFP) levels at 24 weeks after the end of treatment (EOT) were significantly lower, and the platelet count at 24 weeks after the EOT was significantly higher in patients with fibrosis regression than in those without. Logistic regression analysis confirmed that lower AFP levels (< 5.4 ng/mL) at 24 weeks after the EOT (odds ratio [OR], 4.626; 95% confidence interval [CI], 1.557-13.153; P = 0.006) and HCV genotype 2 (OR, 2.198; 95% CI, 1.010-4.786; P = 0.047) were significant independent predictive factors for regressed fibrosis after SVR. CONCLUSIONS: Lower post-treatment AFP levels and HCV genotype 2 significantly correlated with liver fibrosis regression after SVR.

Progressive fibrosis significantly correlates with hepatocellular carcinoma in patients with a sustained virological response.

AIM: Hepatocellular carcinoma develops even in some patients who achieve a sustained virological response following treatment for hepatitis C virus infection. This study investigated the relationship between changes in fibrosis, as assessed by sequential biopsies, and development of hepatocellular carcinoma in patients who achieved a sustained virological response for hepatitis C virus. METHODS: We enrolled 97 patients with sustained virological response who had undergone initial biopsies before therapy and sequential biopsies at an average of 5.8 ± 1.9 years after the initial biopsy. Factors associated with hepatocellular carcinoma were retrospectively analyzed. RESULTS: The liver fibrotic stage regressed in 44 patients (45%), remained stable in 47 patients (48%) and progressed in six patients (6%). The fibrotic stage significantly decreased, from 1.54 ± 0.86 to 1.16 ± 1.07 units. Hepatocellular carcinoma was identified in 12 patients (12.4%). The cumulative incidence of hepatocellular carcinoma in patients with progressive fibrosis was significantly higher than that in patients with regressed or stable fibrosis (P < 0.001). A Cox proportional hazards regression analysis confirmed that progressive fibrosis in sequential liver biopsies (hazard ratio [HR], 8.30; P = 0.001) and low platelet counts before treatment (HR, 8.69; P = 0.006) were significant independent factors associated with the development of hepatocellular carcinoma in patients with a sustained virological response. CONCLUSION: Progressive fibrosis, assessed by sequential biopsies, was significantly correlated with development of hepatocellular carcinoma in patients who had achieved a sustained virological response for hepatitis C virus.

A Predictive Strategy for Nonsurgical Management of Pancreatic Stones.

OBJECTIVES: We set out to predict whether nonsurgical treatment is likely to succeed in removing pancreatic stones in a given patient and also to determine an optimal maximal number of extracorporeal shock wave lithotripsy (ESWL) sessions for treatment of pancreatolithiasis in that patient. MATERIALS AND METHODS: We ascertained the number of ESWL sessions for each of 164 patients undergoing that treatment for pancreatolithiasis between 1992 and 2020. Median follow-up duration was 31 months (range, 0-239), median age was 58 years (22-83), and the male to female ratio was 5.1:1.0. Patients were divided into 2 groups based upon an optimal maximal number of ESWL sessions determined by receiver operating characteristic analysis. RESULTS: Total stone clearance was achieved in 130 of 164 patients (79%). The median number of ESWL sessions was 3 (1-61). Receiver operating characteristic analysis determined 7 to be the optimal maximal number of sessions. Complete clearance was more frequent (87%) among the 131 patients requiring 7 or fewer ESWL sessions than among the 33 undergoing more (48%, P < 0.001). Seventeen patients (52%) undergoing 8 or more sessions still had residual stones. CONCLUSIONS: If any pancreatic stones persist after 7 ESWL sessions, we recommend transition to medical or surgical treatments.

Successful pancreatectomy after conversion-intended chemotherapy using gemcitabine and nab-paclitaxel for unresectable adenosquamous carcinoma of the pancreas: a case report.

BACKGROUND: Adenosquamous carcinoma of the pancreas (ASCP) accounts for only 1-4% of all pancreatic exocrine cancers and has a particularly poor prognosis. The efficacy of chemotherapy for ASCP remains unknown because of the small number of cases, and few studies have evaluated conversion-intended chemotherapy. CASE PRESENTATION: A 76-year-old woman was referred to our hospital because of epigastric pain and nausea. A preoperative contrast-enhanced multidetector row computed tomography (MDCT) scan revealed a 17 × 17 mm low-density tumor with an ill-defined margin at the arterial phase in the pancreatic head. The tumor involved the common hepatic artery, left hepatic artery bifurcated from the common hepatic artery, and gastroduodenal artery, and was in contact with the portal vein. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed an uptake in the pancreatic head but no evidence of distant metastasis. The tumor was diagnosed as an adenocarcinoma of the pancreatic head and staged unresectable because the common and left hepatic arteries were involved. Hence, the patient underwent seven courses of conversion-intended chemotherapy using gemcitabine and nab-paclitaxel for pancreatic ductal adenocarcinoma over 7 months. After chemotherapy, the tumor shrank to 10 × 10 mm on contrast-enhanced MDCT. Consequently, the boundary between the tumor and major vessels of the common and left hepatic arteries and the portal vein became clear, and the involvement of the arteries with the tumor was evaluated to be released. The contact of the tumor to the portal vein also reduced to less than half the circumference of the portal vein. FDG-PET showed decreased accumulation in the tumor. Hence, the tumor was judged resectable, and pancreaticoduodenectomy was performed. The tumor and major blood vessels were easily dissected and R0 resection was achieved. The patient experienced no major complications and was discharged on postoperative day 28. The tumor was revealed as ASCP via pathological examination. The patient is alive and recurrence-free seven months after surgery. This is the first report of successful R0 resection for an initially unresectable ASCP following conversion-intended chemotherapy using gemcitabine and nab-paclitaxel regimen. CONCLUSIONS: Conversion-intended chemotherapy using gemcitabine and nab-paclitaxel regimen may be effective for ASCP.

Large or multiple pseudocysts can impede or complicate the nonsurgical treatment of pancreatolithiasis.

Objectives: We aimed to determine when a coexisting pseudocyst was likely to complicate the nonsurgical treatment of pancreatolithiasis. Methods: We treated 165 patients with pancreatolithiasis nonsurgically between 1992 and 2020, including 21 with pseudocysts. Twelve patients had a single pseudocyst less than 60 mm in diameter. Pseudocysts in the other nine patients had diameters of at least 60 mm or were multiple. The locations of pseudocysts along the length of the pancreas varied from the area with stone involvement to the pancreatic tail. We compared the outcomes in these groups. Results: We found no significant differences in pain relief, stone clearance, stone recurrence, or the likelihood of adverse events between pseudocyst groups or between patients with vs without pseudocysts. However, 4 of 9 patients with large or multiple pseudocysts required transition to surgical treatment (44%) compared with 13 of 144 patients with pancreatolithiasis and no pseudocyst (9.0%) (P=0.006). Conclusions: Patients with smaller pseudocysts typically underwent nonsurgical stone clearance successfully with few adverse events, similar to findings in patients with pancreatolithiasis and no pseudocysts. Pancreatolithiasis complicated by large or multiple pseudocysts did not cause more adverse events but was more likely to require transition to surgery compared with pancreatolithiasis without pseudocysts. In patients with large or multiple pseudocysts, early transition to surgery should be considered when nonsurgical treatment is ineffective.

Large Inflammatory Myofibroblastic Tumor of the Esophagus: A Case Report and Literature Review.

Inflammatory myofibroblastic tumor (IMT) is a rare tumor composed of myofibroblasts with inflammatory blood cell infiltration. It commonly occurs in the lungs and rarely in the esophagus. We herein report a valuable case of IMT originating in the esophagus. A 60-year-old Japanese woman with dysphagia had a large subepithelial lesion in the cervical esophagus, which was 15 cm in length. Surgical resection was performed to confirm the pathological diagnosis and improve the symptoms. The postoperative diagnosis was IMT composed of multiple nodules. There was no recurrence or metastasis within one year after surgery.

Prevalence of hepatitis C virus genotype 1a in Japan and correlation of mutations in the NS5A region and single-nucleotide polymorphism of interleukin-28B with the response to combination therapy with pegylated-interferon-alpha 2b and ribavirin.

Hepatitis C virus (HCV) genotype 1a is rare in Japanese patients and the clinical characteristics of this genotype remain unclear. The interferon (IFN) sensitivity-determining region (ISDR) and single-nucleotide polymorphisms (SNPs) of interleukin-28B (IL28B) among patients with HCV genotype 1b are associated with IFN response, but associations among patients with genotype 1a are largely unknown. This study investigated the clinical characteristics of genotype 1a and examined whether genomic heterogeneity of the ISDR and SNPs of IL28B among patients with HCV genotype 1a affects response to combination therapy with pegylated-IFN-α2b and ribavirin. Subjects comprised 977 patients infected with HCV genotype 1, including 574 men and 412 women (mean age, 55.2 ± 10.6 years). HCV was genotyped by direct sequencing of the 5'-untranslated region and/or core regions and confirmed by direct sequencing of the NS5A region. HCV genotypes 1a (n = 32) and 1b (n = 945) were detected. Twenty-three (71.9%) of the 32 patients with genotype 1a were patients with hemophilia who had received imported clotting factors. Prevalence of genotype 1a after excluding patients with hemophilia was thus 0.9%. Of the 23 patients with genotype 1a who completed IFN therapy, 11 (47.8%) were defined as achieving sustained virological response. Factors related to sustained virological response by univariate analysis were IL28B and ISDR. In conclusion, HCV genotype 1a is rare in Japan. The presence of IL28B genotype TT, and more than two mutations, in the ISDR are associated with a good response to IFN therapy in patients with HCV genotype 1a.

Pancreatic Stones: Clinical Outcomes With Nonsurgical Treatment in a Japanese Single-Center Study.

OBJECTIVES: While chronic pancreatitis associated with pancreatolithiasis presents with pain, exocrine and endocrine pancreatic functions worsen with time. We examined outcomes of nonsurgical treatment. METHODS: Between 1992 and 2020, we treated pancreatolithiasis nonsurgically in 165 patients with chronic pancreatitis using extracorporeal shock wave lithotripsy alone or followed by endoscopic procedures. The mean follow-up duration was 49 months (standard deviation, 56 months) and the age was 56 years (standard deviation, 13 years). The male:female ratio was 5.1:1 (138 men, 27 women). We followed treatment results including relief of abdominal pain, stone clearance and recurrence, and pancreatic exocrine function (bentiromide-p-aminobenzoic acid testing). RESULTS: Treatment relieved pain in 117 of 124 patients (94%). The overall stone clearance was achieved in 130 of 165 patients (79%). Stones recurred during follow-up in 50 of 130 patients (38%). One fifth of recurrences were early, often involving stricture of the main pancreatic duct. After 1 year, 65% of the patients had improved or stable exocrine function. CONCLUSIONS: Nonsurgical stone removal usually improved symptoms and preserved pancreatic exocrine function. Nonsurgical treatment with extracorporeal shock wave lithotripsy followed by endoscopic treatment if needed is useful as initial management for pancreatolithiasis.

Benefit From Nonsurgical Treatment for Asymptomatic Pancreatolithiasis.

OBJECTIVE: Clinical guidelines consider abdominal pain an indication for nonsurgical treatment of pancreatolithiasis. We examined benefit from nonsurgically treating asymptomatic pancreatolithiasis. METHODS: We retrospectively reviewed 165 patients with pancreatolithiasis who underwent nonsurgical treatment between 1992 and 2020. Symptoms were absent in 41, while 124 had abdominal pain. In the asymptomatic group, the median follow-up duration was 8 months (range, 0-166 months), and the median age was 61 years (range, 32-80 years). In patients with pain, the median follow-up duration was 43 months (range, 0-293 months), while the median age was 57 years (range, 22-80 years). The male:female ratio was 3.6:1 for asymptomatic patients and 5.9:1 for those with pain. We compared treatment outcome, stone recurrence rate, and changes in pancreatic exocrine function (bentiromide- p -aminobenzoic acid test results) between groups. RESULTS: Nonsurgical treatment for patients with asymptomatic pancreatolithiasis had a 63% stone clearance rate, lower than 84% for symptomatic pancreatolithiasis but comparable to outcomes at other institutions. Pancreatic exocrine function values during the year after treatment were mean, 52% (standard deviation, 16%) in the asymptomatic group, similar to mean, 57% (standard deviation, 17%) in the symptomatic group. CONCLUSIONS: Nonsurgical treatment in asymptomatic pancreatolithiasis may preserve pancreatic exocrine function as well as in symptomatic pancreatolithiasis.

Nonsurgical treatment for asymptomatic pancreatolithiasis is meaning: A case report.

BACKGROUND: Many guidelines for nonsurgical treatment of pancreatolithiasis suggest little guidance for patients with pancreatolithiasis who do not have abdominal pain. Some patients with pancreatolithiasis whom we have treated nonsurgically with extracorporeal shock-wave lithotripsy did not have abdominal pain, and we describe one of them here. METHODS AND RESULTS: A 42-year-old man complaining of an 8-kg weight loss over 6 months was admitted to a nearby hospital, where fasting blood sugar and hemoglobin A1c values were 500 mg/dL and 11.8%. Computed tomography showed stones in the head of the pancreas and dilation of the main pancreatic duct. He was referred to our hospital to be considered for nonsurgical treatment of pancreatolithiasis. His height and weight were 160 cm and 52 kg (body mass index, 20.31). No tenderness or other abdominal findings were evident. After obtaining informed consent for nonsurgical treatment despite absence of abdominal pain, we performed extracorporeal shock wave lithotripsy. Computed tomography showed disappearance of stones from the pancreatic head. At discharge, his weight had increased to 62 kg and hemoglobin A1c was 6.8%, though antidiabetic medication has since become necessary. CONCLUSION: We believe that nonsurgical treatment of pancreatolithiasis was helpful for this patient, and could improve exocrine and endocrine function in other patients without abdominal pain.

B-mode ultrasonographic diagnosis in gallbladder wall thickening.

Diseases associated with gallbladder wall thickening include benign entities such as adenomyomatosis of the gallbladder, acute and chronic cholecystitis, and hyperplasia associated with pancreaticobiliary maljunction, and also cancer. Unique conditions such as sclerosing cholecystitis and cholecystitis associated with immune checkpoint inhibitor treatment can also manifest as wall thickening, as in some systemic inflammatory conditions. Gallbladder cancer, the most serious disease that can show wall thickening, can be difficult to diagnose early and to distinguish from benign causes of wall thickening, contributing to a poor prognosis. Differentiating between xanthogranulomatous cholecystitis and gallbladder cancer with wall thickening can be particularly problematic. Cancers that thicken the wall while coexisting with benign lesions that cause wall thickening represent another potential pitfall. In contrast, some benign gallbladder lesions that can cause wall thickening, such as adenomyomatosis and acute cholecystitis, typically show characteristic ultrasonographic features that, together with clinical findings, permit easier diagnosis. In this review of the literature, we describe B-mode abdominal ultrasonographic diagnosis of gallbladder lesions showing wall thickening.