Effect of adding daclatasvir in sofosbuvir-based therapy in genotype 3 hepatitis C: real-world experience in Pakistan.

OBJECTIVE: To determine real-world effect of adding daclatasvir (DCV) to chronic hepatitis C treatment by comparing sustained viral response of sofosbuvir (SOF)/DCV±ribavirin (RBV) and SOF+RBV combination in patients with genotype 3 hepatitis C. PATIENTS AND METHODS: Patients with chronic hepatitis C, genotype 3, presenting at the DHMC Hepatology Clinic from October 2014 till March 2018 were treated initially with 6 months of SOF/RBV, and once DCV was available, with SOF/DCV±RBV for 3 or 6 months. Negative hepatitis C virus RNA by PCR, sustained viral response 12 weeks after treatment (SVR12), was the primary end point for per-protocol analysis. RESULTS: The mean age of the 440 enrolled patients was 51.04 (±11.9) years, and male to female ratio was 0.97/1 (217/223). Liver cirrhosis was present in 260 (59.1%) patients, and 89 (20.2%) had decompensated liver disease. Treatment-experienced patients were 124 (28.2%). We included 398 (90.4%) patients with completed follow-up in final analysis, excluding either dropped out, failed to complete therapy or died during follow-up. SVR12 was achieved in 366 (91.9%), being significantly lower (P=0.001) in patients with cirrhosis at 89.9% (205/228), and even lower SVR12 (P=0.006) in decompensated cirrhosis at 87.01% (67/77). SVR12 was also inferior (P=0.005) in treatment experienced patients at 85.8% (97/113) than treatment-naive patients at 94.3% (269/285). Among 285 patients treated with SOF/RBV, SVR12 was achieved in 264 (92.6%), which is not significantly different from SVR12 with SOF/DCV±RBV at 90.2% (102/113) (P=0.57). CONCLUSION: In patients with chronic hepatitis C genotype 3, SOF/RBV and SOF/DCV±RBV have similar sustained viral response, and patients with liver cirrhosis and past treatment experience have suboptimal response in Pakistan.

Cephalosporin resistance in community acquired spontaneous bacterial peritonitis.

OBJECTIVE: To determine 3rd generation cephalosporin resistance in patients with community-acquired spontaneous bacterial peritonitis (SBP) using early response assessment. METHODS: This prospective quasi-experimental study was carried out at Doctors Hospital & Medical Center from January 2016 to September 2018. Patients with cirrhosis and SBP were included. Third generation cephalosporins i.e. cefotaxime/ceftriaxone were used for treatment of SBP. Response after 48 hours was assessed and decline in ascitic fluid neutrophil count of < 25% of baseline was labelled as cephalosporin resistant. Carbapenem were used as second line treatment. Recovery and discharge or death of patients were primary end points. RESULTS: Male to female ratio in 31 patients of SBP was 1.2/1 (17/14). Hepato-renal syndrome was diagnosed in 11(37.9%) patients. Cefotaxime was used for 16(51.6%) patients whereas ceftriaxone for 15(48.3%) patients. Early response of SBP was noted in 26(83.8%) patients while 5 (16.2%) were non-responders to cephalosporins. SBP resolved in all non-responding patients with i/v carbapenem. In-hospital mortality was 12.9% and had no association with cephalosporin resistance. High bilirubin (p 0.04), deranged INR (p 0.008), low albumin (p 0.04), high Child Pugh (CTP) score (p 0.03) and MELD scores (p 0.009) were associated with in-hospital mortality. CONCLUSION: Cephalosporin resistance was present in 16.2% of study patients with community-acquired SBP. Mortality in SBP patients is associated with advanced stage of liver disease.

Pneumatic Balloon Dilatation for Achalasia Cardia; Early & late results, a single center study.

OBJECTIVE: Achalasia Cardia is treated by Pneumatic balloon dilatation, Heller's Myotomy and recently, by Peroral Esophagaeal Myotomy. This study reports the efficacy of pneumatic balloon dilatation as a non-surgical motility in achieving relief of dysphagia, clinical improvement and recurrence. Long-term complications were reported. METHODS: Eight hundred ninety two adult achalasia patients of both genders were treated from January 1988 till December 2011, with pneumatic balloon (Rigiflex Microvasive®) dilatation, under fluoroscopy Barium swallow was obtained prior to and five minutes after dilatation to evaluate for efficacy of dilatation as well as for complications. Patients not responding to 30 mm balloon had repeat dilatation with 35 mm balloon after 8 weeks. All patients were enrolled in regular follow up at one, six months and yearly intervals up to a period of five years. Recurrence was defined as an increase in symptom score at 8 weeks greater than 50% of their baseline value. These patients were treated with 35 mm balloon or referred for surgical intervention. RESULTS: Of 892 patients, follow up was obtained in 50% for 5 years, 9.2% for 4-years), 9.3% for 3-years, 10% for 2-years and 21.5% for 1-year of patients. One patient died after repeat dilatation. Eighty-eight patients were excluded from this analysis (20 died due to non-procedure related causes and another 68 were lost during follow up). Statistically significant improvement was noted in reduction in height and width of barium column and symptom score coupled with weight gain during follow up. Forty-eight patients were subjected to repeat dilatation with 35 mm balloon, two of these developed post-procedure perforations with one mortality. Three non-responsive patients required surgical laparoscopic myotomy. No carcinoma of esophagus was reported during follow up. One patient post dilatation, developed esophageal bezoar. A single pneumatic dilatation achieved a remission rate of 93% at four years, 90% at three years, 95% at two years and 92% at one year post dilatation. CONCLUSION: Achalasia of esophagus can be effectively and safely treated with balloon dilatation to achieve adequate short and long-term symptomatic relief with a low complication rate.

Sofosbuvir based therapy in hepatitis C patients with and without cirrhosis: Is there difference?

OBJECTIVE: To compare sustained viral response to sofosbuvir/ribavirin ±interferon therapy in patients of hepatitis C with and without liver cirrhosis. METHODS: This observational study of chronic hepatitis C patients was carried out at Doctors Hospital and Medical Center (DH&MC). After diagnostic workup, Sofosbuvir/ribavirin for 24 weeks or sofosbuvir/ribavirin/pegylated interferon for 12 weeks were prescribed. Primary outcome was negative HCV RNA by PCR 12 weeks after treatment completion (SVR12). Chi square χ2 and student's t test were used to analyze data. RESULTS: Of 216 patients included, liver cirrhosis was present in 112 (51.9%) patients and 69(31.9%) were treatment experienced. Liver disease was decompensated in 37 (17.1%) patients. Of 206 patient who completed study protocol, 173(83.1%) achieved SVR12, 89.2% (25/28) with triple therapy and 82.2% (148/180) with sofosbuvir/ribavirin therapy. Treatment response was similar between treatment naïve 86.2% (119/138) and treatment experienced 79.4% (54/68) patents. (p value 0.19) SVR12 was inferior in cirrhosis patients 75.4% (80/106) as compared to those with no cirrhosis 93% (93/100) (p value < 0.000). It was even lesser in those with decompensated liver disease 68.8% (24/35) (p value < 0.000). CONCLUSION: Treatment outcome with sofosbuvir/ribavirin combination therapy in cirrhosis patients is suboptimal especially in those with decompensation as compared to patients without liver cirrhosis.

AAA Syndrome, Case Report of a Rare Disease.

Triple A (Allgrove) syndrome, an autosomal recessive disease is characterized by achalasia, alacrimia and ACTH-resistant adrenal failure with progressive neurological syndrome including central, peripheral and autonomic nervous system impairment, and mild mental retardation. The triple A syndrome gene, designated AAAS, localized on chromosome 12q 13 encodes for a 546 amino acid protein called ALADIN (Alacrimia-Achlasia-Adrenal Insufficiency and Neurologic disorder). This report relates to two sisters, aged 8 and 12 years, who had vomiting, muscle weakness, alacrimia, excessive fatigue and dysphagia. Abdominal sonography, esophago-gastroduodenoscopy, barium swallow, esophageal manometry, CT scan abdomen and brain, biochemical profiles, as well as neurologic and ophthalmic evaluations were consistent with Allgrove's syndrome. Management consisted of pneumatic balloon dilatation for achalasia and initiation of cortisone therapy with successful resolution of dysphagia and other symptoms.

Hepatorenal syndrome:Response to terlipressin and albumin and its determinants.

OBJECTIVE: To determine the efficacy of terlipressin and albumin in improving renal functions in patient with hepatorenal syndrome (HRS) and to identify factors determinant of better response. METHODS: In this quasi experimental interventional study patients of liver cirrhosis and ascites with HRS type I were treated with intravenous albumin and incremental dosage of terlipressin based on response with maximum dose of 12mg/day. Decline of creatinine below 1.5mg/dl was defined as complete response. Factors predictive of response to therapy were determined via linear regression analysis. RESULTS: Twenty four patients were included with male to female ratio 3.8/1(19/5) and mean age 53.3 (±10.06). Complete response to terlipressin/albumin was seen in 14 (58.3%)patients, seven (29.2%) achieved partial response with > 25% creatinine decline while three (12.5%) had no response. Lower serum creatinine at diagnosis (P value 0.003), absence of hyperkalemia (p value 0.005) and absence of portal vein thrombosis (p value 0.05) are associated with response to treatment in HRS. Baseline serum creatinine (p value 0.003) was independent predictor of response to therapy in multivariate analysis. CONCLUSION: Terlipressin and albumin is an effective treatment for HRS type I. Patients with lower baseline serum creatinine are more likely to respond to this therapy.

Response Guided Interferon Therapy for Genotype 3 of Chronic Hepatitis C: Compliance and Outcome.

OBJECTIVE: To determine compliance and improvement in sustained viral response (SVR) by following response guided therapy (RGT) plan of interferon and ribavirin, for genotype 3 in chronic hepatitis C. METHODS: Patients with chronic hepatitis C genotype 3, who were eligible for interferon-ribavirin therapy and consented for RGT, were included. Those with no rapid viral response (RVR), having coarse echotexture of liver or undergoing re-treatment, were advised 48 week treatment whereas, rest had 24 week standard therapy. PCR for HCV RNA checked 6 months after discontinuing treatment, was the primary end point of study. RESULTS: Of 154 patients, included in the study with mean age of 39.9 (±10.84) and male to female ratio 1.4/1 (94/60), majority of patients, 136 (88.4%) were treatment naïve whereas, 18 (11.6%) were being retreated. On ultrasound, 63 (40.9%) patients had coarse liver and 33 (21.4%) had splenomegaly. RVR was achieved in 99 (64.3%) patients. Overall 66(42.8%) patients merited extended duration of therapy as per RGT plan but only 22 (33%) were compliant. Treatment related side effects were the dominant reason for declining RGT in 33 (75%) patients. SVR was noted in 111 (72.1%) patients. Those patients with extended therapy (RGT), had SVR 90.9% (20/22), although, better but statistically not significant than those who stopped therapy at 6 months 77.2% (34/44) (p value 0.11). CONCLUSION: Response guided therapy plan did not improve SVR to pegylatedinterferon and ribavirin therapy in patients with genotype 3 and it has low patient compliance due to treatment related side effects.

Predicting Prognosis in Hepatocellular Carcinoma: Comparison of Staging Systems in Pakistani Cohort.

OBJECTIVE: To determine the clinical, biochemical and radiological prognostic indicators and to compare the performance of six staging systems in patients of hepatocellular carcinoma (HCC). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Gastroenterology, Doctors Hospital, Lahore, from October 2007 to December 2013. METHODOLOGY: Patients with HCC were included. Baseline clinical, hematological and radiological variables were noted. Patients were followed for 5 years or till death. Survival predictors were identified using Cox proportional hazard analysis and 6 prognostic staging systems were evaluated by determining homogeneity, discriminatory ability and monotonicity. RESULTS: Of the 228 patients included, male to female ratio was 2.6/1 (165/63) and mean age was 56.5 ±10.4 years. Majority of patients 189 (82.9%) were anti-HCV positive. Solitary HCC lesion was seen in 121 (53.1%) patients, 16 (7%) had 2 lesions while 73 (32%) had 3 or more lesions. Only 36 (15.8%) patients had palliative therapy for HCC. Survival rate was 45.2%, 25%, 12.3%, 7%, 2.2% and 1% for 6 months, 1, 2, 3, 4 and 5 years respectively. Male gender, portal vein thrombosis, serum albumin < 3.5 g/dl, tumor size ≥6 cm and alpha fetoprotein (AFP) ≥147 U/ml were bad prognostic indicators. OKUDA, GRETCH and early stages of CLIP had better homogeneity while CLIP showed superior discriminatory ability and monotonicity for predicting survival. CONCLUSION: Male gender, presence of portal vein thrombosis, low serum albumin, large tumor size and high AFP level are poor prognostic indicators in patients of HCC. CLIP has better performance in predicting mortality.

16 Y/O Female with "Watermelon Stomach"?

Background. Gastric antral vascular ectasia (GAVE) also known as "watermelon stomach" (WS) is an uncommon cause of gastrointestinal (GI) blood loss. It typically presents in middle aged females. We are presenting a case of GAVE at an unusually early age with atypical symptoms. Case. A previously healthy 16 y/o Caucasian female presented to the ER with a one-month history of upper abdominal pain. Physical examination was benign except tenderness in the epigastric region. There were no significant findings on laboratory data. Upper endoscopy showed incidental findings of linear striae in the antrum indicative of GAVE but histology was equivocal. Discussion. GAVE is a poorly understood but treatable entity and an increasingly identifiable cause of chronic iron deficiency anemia or acute or occult upper GI bleeding. The pathophysiology of GAVE remains unclear. It is an endoscopic finding characterized by longitudinal columns of tortuous red ectatic vessels (watermelon stripes), pathognomonic for WS. Treatment options include endoscopic, pharmacologic, and surgical approaches. Failure to recognize GAVE can result in delayed treatment for years. Our patient with GAVE was unusually young and was diagnosed incidentally. Due to lack of anemia on laboratory examination we elected to monitor her clinically for any future development of anemia.