Hepatitis C Retreatment With First-Line Direct Acting Antiviral Drugs.

Background and Aims: Sofosbuvir (S), daclatasvir (D), ledipasvir, or velpatasvir (V) containing first-line hepatitis C virus (HCV) treatment regimens fail to cure viremia in 5-10%. We report our experience of HCV retreatment using these first-line drugs, in a setting where second-line anti-HCV drugs are not available. Methods: Adults, who had relapsed after first complete course of a sofosbuvir-containing first-line, pegylated interferon free, anti-HCV treatment regimen with or without ribavirin (Riba) were included. Retreatment regimen, tailored to the failed anti-HCV regimen, was based on principle of using first-line drugs for 24 weeks with ribavirin and swapping between pangenotypic and genotype-specific regimens. Retreatment outcome was categorized as successful (achieved undetectable HCV RNA at the end of treatment [ETR] and sustained viral response at week 12 [SVR12]), non-responder (failed to achieve ETR), or relapse (achieved ETR but not achieved SVR12). Results: Twelve patients (9 male; 7 cirrhosis; all genotype 3) who had relapsed to prior anti-HCV treatment (4 SD12, 4 SD24, 1 SDRiba12, 1 SDRiba24, 2 SV12) were included. Following retreatment (2 SDRiba24, 10 SVRiba24), all achieved ETR but only 9 (75%) achieved SVR12. Two among three, in whom retreatment failed, achieved SVR12 following another course of sofosbuvir/velpatasvir/ribavirin for 24 weeks. Overall, 11/12 (92%) patients achieved SVR12 following retreatment with the first-line anti-HCV drugs. Conclusion: HCV retreatment could be a treatment option if second-line anti-HCV drugs are not available. Successful retreatment could be achieved, in a large proportion, with the use of first-line drugs for 24 weeks with ribavirin and swapping of pangenotypic/genotype-specific regimens (NCT03483987).

Abernethy Malformation Masquerading as Congenital Heart Disease: A Boy With Cyanosis, Clubbing, and Hypoxia.

Abernethy malformation is an extrahepatic congenital portosystemic shunt characterized by the diversion of the portal blood away from the liver through a shunt that drains directly into the inferior vena cava. We present a case of a male child with Abernethy malformation, which was initially diagnosed as cyanotic heart disease due to pulmonary arteriovenous malformation. However, after proper clinical evaluation and investigations, the diagnosis of Abernethy malformation was established. Thereafter, the patient was successfully treated with endovascular embolization. At one year follow-up, marked relief in exertional dyspnea and improvement in physical growth was achieved with no observable complications.

Acute hepatitis C treatment in advanced renal failure using 8 weeks of pan-genotypic daclatasvir and reduced-dose sofosbuvir.

BACKGROUND: Sofosbuvir is not recommended in persons with estimated glomerular filtration rate (eGFR) <30 mL/min. We report the results of treatment with an off-label 8-week regimen of daclatasvir and half-dose sofosbuvir in patients with acute infection with hepatitis C virus ( HCV) and eGFR <30 mL/min. METHODS: Clinic records were searched to identify treatment-naïve, noncirrhotic adults with acute hepatitis C (HCV viremia and a ≥10-fold elevation of serum alanine aminotransferase activity) and eGFR <30 mL/min, who had been treated with a sofosbuvir-based regimen. Treatment response was assessed using serum HCV RNA testing at 4 weeks of treatment, end of the 8-week treatment and 12 weeks after stopping treatment. RESULTS: Of the 31 patients with acute hepatitis C, 27 [median age (range): 36 (18-74) years; 20 (74%) male] were started on treatment with 200 mg sofosbuvir and 60 mg daclatasvir daily for 8 weeks, irrespective of HCV genotype. All the 27 completed the planned 8-week treatment. One patient died 10 weeks after completing the treatment of an unrelated cause. All the 27 patients had undetectable HCV RNA after 4 weeks of and at the end of treatment. At 12 weeks after completion of treatment, only one tested HCV RNA positive and 25 were negative, with sustained virological response rate of 25/27 (92.6%) and 25/26 (96.2%) on intention-to-treat and per-protocol basis, respectively. CONCLUSION: Eight-week course of daclatasvir and half-dose sofosbuvir is effective for acute hepatitis C in patients with eGFR <30 mL/min and could be a useful alternative to costly, kidney-safe anti-HCV oral drugs in resource-constrained settings.

Gastric tuberculosis mimicking liver abscess - A case report.

Tuberculosis of the stomach is quite rare, both as a primary or secondary infection. It has varied presentation ranging from non-specific abdominal pain and constitutional symptoms to hematemesis, gastric outlet obstruction and pyrexia of unknown origin. Here, we report a rare, interesting case of locally advanced gastric tuberculosis, which morphologically mimicked liver abscess initially in a young, immunocompetent patient presenting with fever and abdominal pain. The disease was diagnosed by GeneXpert MTB/RIF assay, and responded well to antituberculosis medication without surgery. Clinicians must bear in mind that, even in the absence of immunodeficiency, as in this case, tuberculosis can involve any site in the gastrointestinal tract and may present with a variety of presentation and infiltrating adjacent organ that might be mistaken as malignancy. This is first case report of gastric tuberculosis, which is locally advanced with adjacent liver infiltration initially thought to be left lobe liver abscess.

Viral suppression is comparable with 0.5 mg and 1.0 mg daily doses of entecavir in treatment-naive HBV-related decompensated cirrhosis.

BACKGROUND: For patients with HBV infection who have decompensated cirrhosis (DC), a higher dose (1.0 mg/day) of entecavir is recommended than that used for those with compensated disease (0.5 mg/day), though with very little supporting data. We therefore compared the viral suppression achieved with 0.5 mg/day and 1.0 mg/day of entecavir in patients with HBV-related DC (NCT03345498). METHODS: Treatment-naive patients with HBV-related DC and serum HBV DNA titre exceeding 100,000 IU/ml received either dose of entecavir for 24 weeks. HBV DNA concentration was measured in blood specimens collected at baseline and after 2, 4, 8, 12 and 24 weeks of entecavir treatment. RESULTS: Participants in the 0.5 mg/day (n=13) and 1.0 mg/day (n=16) groups had similar baseline hepatitis B e antigen (HBeAg) positivity rates (12/13 and 12/16; P=0.34) and median (range) log10 serum HBV DNA levels (6.81 [5.01-8.12] and 7.45 [5.24-8.65]; P=0.17). The two doses led to similar reductions in serum HBV DNA levels after 2, 4, 8, 12 and 24 weeks of entecavir administration. At 24 weeks, 3 of the 13 patients receiving 0.5 mg/day and 1 of the 16 patients receiving 1.0 mg/day of entecavir had undetectable serum HBV DNA. Serum albumin level showed significant and similar improvement at the end of 24 weeks in the two groups. CONCLUSIONS: Treatment-naive patients with HBV-related DC can be treated with entecavir in a 0.5 mg/day dose instead of the higher 1.0 mg/day dose, without compromising the degree of virological suppression. ClincialTrials.gov number NCT03345498.

Perforation following pneumatic dilation of achalasia cardia in a university hospital in northern India: A two-decade experience.

Pneumatic dilation (PD) is a cost-effective first-line treatment for achalasia. The most feared complication of PD is esophageal perforation (EP). As data on EP after PD for achalasia are not widely reported, we present the frequency, risk factors, and treatment-outcome of EP. Records of patients undergoing PD for achalasia (January 1995 to September 2015) were retrospectively reviewed. Of 433 patients (age 38 years, 13-88, 57% male), and 521 dilations, 12 were complicated by EP (2.7% of patients and 2.3% of PD). EP occurred in 7 (3.4%), 4 (1.7%), and 1 (4.1%) with use of balloon diameters 30, 35, and 40 mm, respectively. In most (11/12, 92%), EP occurred during the first PD. No risk factor for EP was identified (p = 0.65 for the first dilation vs. > 1 dilation, and 0.75 for balloon size of 30 mm vs. > 30 mm). Seven patients with contrast leak on esophagogram and/or computed tomography scan underwent surgery. One other with contrast leak was successfully treated with a fully covered self-expandable metal stent (FC-SEMS); the remaining four with small leak/pneumomediastinum were managed conservatively. The median duration of hospital stay following perforation was 13 days (7-26) and 8 days (6-10) in surgery and conservative groups, respectively. No mortality was observed in either group. The frequency of EP with PD was 2.3%. Though most EP (92%) occurred during the first dilation, neither the balloon size nor repeated dilations were identified as risk factors. Both surgical and conservative approaches had a favorable outcome in appropriate settings.

Indian consensus on chronic constipation in adults: A joint position statement of the Indian Motility and Functional Diseases Association and the Indian Society of Gastroenterology.

The Indian Motility and Functional Diseases Association and the Indian Society of Gastroenterology developed this evidence-based practice guideline for management of chronic constipation. A modified Delphi process was used to develop this consensus containing 29 statements, which were generated by electronic voting iteration as well as face to face meeting and review of the supporting literature primarily from India. These statements include 9 on epidemiology, clinical presentation, and diagnostic criteria; 8 on pathophysiology; and the remaining 12 on investigations and treatment. When the proportion of those who voted either to accept completely or with minor reservation was 80% or higher, the statement was regarded as accepted. The members of the consensus team believe that this would be useful for teaching, clinical practice, and research on chronic constipation in India and in other countries with similar spectrum of the disorders.

Constipation in degenerative cervico-thoracic spine myelopathy: a simple co-existence or a complex inter-relationship?

PURPOSE: Identify factors affecting constipation and post surgical improvement in patients of myelopathy. METHODS: Sixty-four patients with myelopathy due to extradural spine pathologies (47 cervical; 17 thoracic spine, male:female-5.4:1 with mean age 46.16) underwent evaluation including Bristol stool scale (BSS), PFT and uroflowmetry. All cases were evaluated by gastroenterologist to rule out any intrinsic bowel disease. Chi-square test, Kruskal-Wallis/Mann-Whitney U test and Wilcoxon signed rank test were employed to ascertain statistical significance. RESULTS: The presence of constipation was associated with male sex (p = 0.01), degree of constipation with duration bladder symptoms (p = 0.008) and numbness (p = 0.04). The improvement in BSS after surgery (p = 0.006) was associated with local pain (p = 0.02), duration of weakness (p = 0.04) and overall symptoms (p = 0.01), also with pulmonary function tests (p = 0.002) and pre-operative Nurick's grade (p = 0.01). CONCLUSION: Constipation is a myelopathic symptom as it is relieved by cord decompression and the gender, PFT and the duration of symptoms play an important role in defining constipation and expected improvement in these patients.

Biodegradable Stents for Caustic Esophageal Strictures: Do They Work?

Biodegradable (BD) stents have been used for the management of various esophageal strictures (ES) but the experience of its use in caustic strictures is limited. The present study, aimed at evaluating efficacy of BD stents for the treatment of refractory caustic-induced ES, was a retrospective multi-center study conducted at three tertiary care centers in India wherein adult patients with refractory caustic induced strictures underwent placement of a BD stent. Patients were followed up for immediate complications and long term outcome. All 13 patients (39.3 ± 15.1 years) underwent successful BD stent placement. Retrosternal chest pain occurred in 2 patients and stent migration in 1 (7.6%) patient. At 3 months, restenosis with recurrence of dysphagia was seen in nine (69.2%) patients, at 6 months, 10 (77%) patients had dysphagia of whom three underwent surgery and the remaining seven patients required dilatations. At 1 year, one patient remained asymptomatic while nine had dysphagia. The requirement for dilatation was once in 3 months in seven patients & once in a month in two patients. At 2 years, the requirement of dilatations was further reduced to once in 4-6 months in all patients. Over a 3 year follow up three (23%) patients had undergone surgery, one was free of symptoms while nine patients continued to be on periodic dilatation although the requirement had reduced to once in 4-6 months. Efficacy of BD stents in patients with caustic-induced ES is limited and the short term radial force applied by the currently available BD stents is inadequate to provide long term relief in such patients.

Effect of biofeedback therapy on anorectal physiological parameters among patients with fecal evacuation disorder.

BACKGROUND: Though biofeedback therapy is often effective in patients with fecal evacuation disorder (FED), a common cause of chronic constipation (CC) in tertiary practice, data on anorectal physiological parameters following it are scanty. METHODS: Consecutive patients with FED with CC diagnosed by abnormalities in at least two of the three tests (anorectal manometry, defecography, and balloon expulsion test [BET]) undergoing biofeedback (two sessions per day, 30 min each, for 2 weeks) during a 3-year period were analyzed. Clinical evaluation, anorectal manometry (ARM), and BET were performed at the beginning and after biofeedback. RESULTS: Incomplete evacuation 42/43 (98%), straining 40/43 (93%), and feeling of outlet obstruction 35/43 (81%) were the most common symptoms among these 43 patients (median age 44 years, range 18-76, 30 [71%] male). All the three tests (defecography, BET, and ARM) were abnormal in 17 (40%) patients and the others had two abnormal tests. Improvement in physiological parameters was noted following biofeedback (median residual anal pressure during defecation 99 mmHg (range 52-148) vs. 78 mmHg (37-182), p = 0.03; maximum intra-rectal pressure 60 mmHg (90-110) vs. 76 mmHg (31-178); p = 0.01; defecation index 1.1 (0.1-23.0) vs. 3.2 (0.5-29.0); p = 0.001). Dyssynergia on ARM and BET got corrected in 22/34 (65%) and 18/30 (60%) patients. At a 1-month follow up, 23/37 (62%) patients reported satisfactory symptomatic improvement. CONCLUSIONS: Biofeedback not only improves symptoms but also anorectal physiological parameters in patients with FED.

Mapping of Brain Activations to Rectal Balloon Distension Stimuli in Male Patients with Irritable Bowel Syndrome Using Functional Magnetic Resonance Imaging.

BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is associated with exaggerated cerebral response including emotional processing following visceral stimulation; though data on this issue is available in female IBS patients, it is scanty among males. Hence, we aimed to study brain response of male IBS patients following rectal balloon distension as compared to healthy controls using functional magnetic resonance imaging (fMRI). Data between diarrhea and constipation predominant IBS (IBS-D and IBS-C) were also compared. METHODS: Rectal balloon distension threshold was assessed in 20 male IBS patients (10 IBS-C and 10 IBS-D) and 10 age-matched male healthy controls. Subsequently, fMRI on all the participants was performed at their respective rectal pain threshold. The fMRI data were analysed using the Statistical Parametric Mapping software. RESULTS: IBS patients showed greater cerebral activations in insula, middle temporal gyrus, and cerebellum in the left hemisphere compared to healthy controls. Neural activation was found in bilateral precuneus/superior parietal lobules in controls but not in patients with IBS. The brain activation differed among IBS-C and IBS-D patients; while the right mid-cingulate cortex was activated in IBS-C, the left inferior orbito-frontal cortex, left calcarine, and bilateral fusiform gyri were activated among patients with IBS-D following rectal balloon distension. CONCLUSIONS: Brain response to rectal balloon distension differed among male patients with IBS and controls and among patients with IBS-C and IBS-D. Differential activation among patients with IBS-C and IBS-D was seen in the brain regions controlling affective motivation, homeostatic emotions, and autonomic responses to pain.

Esophageal Acidification During Nocturnal Acid-breakthrough with Ilaprazole Versus Omeprazole in Gastroesophageal Reflux Disease.

BACKGROUND/AIMS: Though nocturnal acid-breakthrough (NAB) is common in gastroesophageal reflux disease (GERD) patients, its clinical importance results from esophageal acidification, which has been shown to be uncommon. Ilaprazole, a long-acting proton pump inhibitor, may cause NAB infrequently. Accordingly, we studied prospectively, (1) frequency and degree of esophageal acidification during NAB, and (2) frequency and severity of NAB while on ilaprazole versus omeprazole. METHODS: Fifty-eight consecutive patients with GERD on once daily ilaprazole, 10 mg (n = 28) or omeprazole, 20 mg (n = 30) for > one month underwent 24-hour impedance-pH monitoring prospectively. NAB was defined as intra-gastric pH < 4 for > one hour during night, and esophageal acidification as pH < 4 for any duration. Nocturnal symptoms (heartburn, regurgitation, and chest pain) were also recorded. RESULTS: Of the 58 patients (age 35.5 [inter-quartile range 26.5-46.0] years, 38 [65.5%], 42 (72.4%) had NAB. Though patients with NAB had lower nocturnal intra-gastric pH than without (2.8 [1.9-4.1] vs 5.7 [4.6-6.8], P < 0.001), frequency and duration of nocturnal esophageal acidification (17/42 vs 4/16, P = 0.360 and 0.0 [0.0-1.0] vs 0.0 [0.0-0.3] minutes, P = 0.260, respectively) and symptoms were comparable (13/42 vs 6/16, P = 0.750). Though ilaprazole was associated with less NABs (1 [range 1-2, n = 19] vs 1 [range 1-3, n = 23], P = 0.010) than omeprazole, the frequency, duration, and mean intra-gastric pH during NAB were comparable (19/28 vs 23/30, P = 0.560; 117 [0-315] vs 159 [69-287] minutes, P = 0.500; 1.02 [0.7-1.4] vs 1.04 [0.44-1.3], P = 0.620, respectively). CONCLUSIONS: Though NAB was common while patients were on a proton pump inhibitor, esophageal acidification was uncommon. Frequency and severity of NAB were comparable among patients on ilaprazole and omeprazole, except for the lesser number of NABs with ilaprazole.

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016.

India contributes significantly to the global burden of HCV. While the nucleoside NS5B inhibitor sofosbuvir became available in the Indian market in March 2015, the other directly acting agents (DAAs), Ledipasvir and Daclatasvir, have only recently become available in the India. The introduction of these DAA in India at a relatively affordable price has led to great optimism about prospects of cure for these patients as not only will they provide higher efficacy, but combination DAAs as all-oral regimen will result in lower side effects than were seen with pegylated interferon alfa and ribavirin therapy. Availability of these newer DAAs has necessitated revision of INASL guidelines for the treatment of HCV published in 2015. Current considerations for the treatment of HCV in India include the poorer response of genotype 3, nonavailability of many of the DAAs recommended by other guidelines and the cost of therapy. The availability of combination DAA therapy has simplified therapy of HCV with decreased reliance of evaluation for monitoring viral kinetics or drug related side effects.