Initial results of efficacy and safety of sofosbuvir among Pakistani population: a real life trialhepatitis eradication accuracy trial of sofosbuvir [HEATS]

Objective: The uridine nucleotide analogue sofosbuvir is a selective inhibitor of hepatitis C virus [HCV] NS5B polymerase approved for the treatment of chronic HCV infection with genotypes 1 - 4. The objective of the study was to evaluate the interim results of efficacy and safety of regimens containing Sofosbuvir [Zoval] among Pakistani population with the rapid virologic response [RVR2/4 weeks] with HCV infections

Methods: This is a multicenter open label prospective observational study. Patients suffering from chronic Hepatitis C infection received Sofosbuvir [Zoval] 400 mg plus ribavirin [with or without peg interferon] for 12/24 weeks. The interim results of this study were rapid virological response on week 4. Data was analyzed using SPSS version 21 for descriptive statistics

Results: A total of 573 patients with HCV infection were included in the study. The mean age of patients was 46.07 +/- 11.41 years. Out of 573 patients 535 [93.3%] were treatment naive, 26 [4.5%] were relapser, 7 [1.2%] were non-responders and 5 [1.0%] were partial responders. A rapid virologic response was reported in 563[98.2%] of patients with HCV infection after four weeks of treatment. The treatment was generally well tolerated

Conclusion: Sofosbuvir [Zoval] is effective and well tolerated in combination with ribavirin in HCV infected patients

Development of systemic lupus erythematosus following interferon-alpha therapy for hepatitis C infection

Interferon-alpha [IFN-alpha] therapy has been associated with de novo development of systemic lupus erythematosus [SLE]. We report a 48-year woman with chronic hepatitis C, who developed low grade fever, joint aches and pains, painful mouth ulcers, shortness of breath, dry cough and pleuritic chest pain after 2 months of completion of treatment with pegylated interferon-alpha. These clinical manifestations and the relevant immunologic investigations were in favour of SLE. She responded well to corticosteroids and hydroxychloroquine treatment

Quality of colonoscopy and spectrum of lower gastrointestinal disease as determined by colonoscopy

To document the quality of colonoscopy practice and the pattern of colonic disease including polyp detection rate at Shifa International Hospital, Islamabad, Pakistan. An observational study. Shifa International Hospital, Islamabad, Pakistan, from May 2013 to June 2014. This retrospective study recorded demographics of patients, indications and quality indices of 505 colonoscopies performed during the study period. Preparation was done with low residue diet and polyethylene glycol. Conscious sedation was generally used. Quality indices studied were compared with guideline standard. Out of 505 colonoscopy patients, 305 were males and 200 were females. The indications for colonoscopic examination were lower gastrointestinal bleeding [26.5%, n=134], screening for colorectal cancer [14.1%, n=71], chronic diarrhea [12.9%, n=65], abdominal pain [10.9%, n=55], anemia [9.1%, n=46], constipation [7.3%, n=37], hematochezia and diarrhea [6.3%, n=32], altered bowel habits [5.1%, n=26], weight loss [3.6%, n=18], colonic thickening on CT scan [3.0%, n=15] and others [1.2%, n=6]. Bowel preparation was adequate [in 92%, n=465] cases. Cecal intubation rate was 88.71% [n=448]. Endoscopic diagnoses were hemorrhoids [36.2%, n=183], normal [22%, n=111], polyps [11.3%, n=57], ulcerative colitis [8.7%, n=44], cancer [4%, n=20], diverticulosis [3.4%, n=17], infective colitis [2.6%, n=13], intestinal TB [2.6%, n=13], non-specific colitis [2.2%, n=11], proctitis [1.8%, n=9] and others [5.3%, n=27]. There is room for improvement in quality of colonoscopy, cecal intubation rate is slightly below the recommended standard and polyp detection rate is quite low however, it is not clear if the low rate of polyp detection is due to missed lesions or low population incidence. Time to reach caecum and withdrawal time should clearly be documented in the notes which can help to evaluate quality of the procedure in a better way

Cancer antigen-125 as a marker of ascites in patients with liver cirrhosis

To evaluate the correlation between Cancer Antigen-25 [CA-125] levels with the amount of ascites in patients with liver cirrhosis. Observational, analytical study. Shifa International Hospital, Islamabad, from March 2012 to February 2013. A total of 130 patients with liver cirrhosis [with and without ascites] had serum CA-125 levels measured. The amount of ascites was classified according to physical examination and ultrasound [USG] findings. CA-125 levels were compared and correlated with amount of ascites. Majority of patients [57%] had hepatitis C virus and 60% were in class Child Pugh C. There was moderate correlation between amount of ascites and CA-125 levels [r = 0.642, p < 0.001] with significant raised levels of CA-125 in patients with ascites [p < 0.001]. There was a moderate correlation between CA-125 levels and presence and amount of ascites.

Frequency of occult hepatitis B in patients awaiting liver transplant

Some patients do not have conventional markers of hepatitis B i.e. HBsAg, HBeAg. However, they may still carry viral DNA. This group of patients who got negative HBsAg but detectable HBV DNA by PCR is defined to have occult hepatitis B [OHB]. Occult hepatitis B can reactivate and affect transplanted liver when given immunosuppressants. To determine the frequency of occult hepatitis B in patients on waiting list for liver transplant in Shifa International Hostpital, Islamabad, Pakistan. Prospective non-interventional study was carried out at Gastroenterology unit of Shifa International Hospitals, Islamabad from April 2012 to May 2013. Materials and One hundred and twenty three patients on the waiting list for liver transplant were included in the study after fulfilling inclusion criteria. All the baseline laboratory tests including complete hepatitis profile HBsAg, HBc IgM and IgG, Anti HCV and HBV DNA by PCR were performed. Data were collected in specially designed proforma. All the data were analyzed using SPSS version 16.0. Out of 123 patients, 67[54.4%] were male and 56[45.5%] were female. Mean age was 52.7 +/- 11.06. Nine [7.31%] patients were found to have occult hepatitis B. Out of these 9 patients, 5[55%] had HCV as primary cause of their liver disease, 2[22%] had HCC and 2[22%] had cryptogenic liver disease, which is diagnostic of exclusion. Occult hepatitis B is the ignored entity in Pakistan. Our study showed that occult hepatitis B was detectable in our population with liver disease. It is important to check its presence in all patients of chronic liver disease regardless of the primary aetiology of liver disease

Renal failure in patients with end stage liver disease and its impact on clinical outcome

To evaluate the prevalence of renal failure [RF] in the patients of end stage liver disease [ESLD], to determine the causes of RF in these patients and its impact on patient's outcome. Descriptive, analytical study. Shifa International Hospital, Islamabad, Pakistan, from May 2011 to March 2013. A total of 523 patients with end stage liver disease [ESLD] were evaluated, renal failure [RF] and its causes were recognized in these patients according to established criteria. Outcome of these patients was assigned as reversal of RF or mortality. Data was analyzed using SPSS version 16. Chi-square test was used for comparing proportions and t-test was used for comparing mean values. P < 0.05 was considered significant. Out of 523 patients, 261 [49.9%] had RF. Acute kidney injury [AKI] was the most common presentation seen in 160 [61%] patients. Hypovolemia and infections were the most frequent causes of RF. Mortality was significantly higher in the patients with RF, when compared to the patients without RF [31% vs. 4.5%, p < 0.001]. Reversal of RF was seen in 98 [37%] of the affected patients. Reversal was more common in the patients with hypovolemia. The mortality was higher in the patients with hepatorenal syndrome [HRS] and infections. Renal failure in the end stage liver disease is an important prognostic factor. Etiology of RF is the key factor in patients' outcome. Patients of ESLD with RF had higher mortality. Majority of the cases of RF were reversible in patients of ESLD coming in the setup

Ammonia levels and the severity of hepatic encephalopathy

To evaluate the correlation between ammonia levels with the severity of HE in patients coming to the tertiary care hospital with liver cirrhosis and hepatic encephalopathy [HE]. Descriptive, analytical study. Shifa International Hospital, Islamabad, from January 2011 to February 2012. A total of 135 patients with liver cirrhosis and HE had serum ammonia levels measured on admission. The diagnosis of HE was based on clinical criteria, and its severity was graded according to the West Haven Criteria for grading of mental status. Ammonia levels were correlated with the severity of HE using Spearman rank correlation. Out of 20 patients with normal ammonia levels, 13 [65%] were in HE I-II, 6 [30%] were in grade-III, while 1 [5%] patient was in grade-IV HE. Out of 45 patients with mild hyperammonemia, 27 [60%] were in grade I-II, 12 [26%] were in grade-III and 6 [13%] were in grade-IV HE. Out of 34 patients with moderate hyperammonemia, 9 [26%] were in grade I-II, 18 [53%] were in grade-III, and 7 [20%] were in grade-IV HE. Out of 36 patients with severe hyperammonemia, 31 [86%] patients were in grade-IV HE [p < 0.001]. Ammonia levels correlated with the severity of hepatic encephalopathy. Greater the ammonia level, severe is the grade of hepatic encephalopathy

Correlation of hyponatremia with hepatic encephalopathy and severity of liver disease

To assess the frequency of low serum sodium levels and to correlate it with the severity of liver disease and hepatic encephalopathy [HE] in patients coming to the tertiary care hospital. Observational study. Shifa International Hospital, Islamabad, from January 2011 to January 2012. A total of 202 patients with hepatic encephalopathy and chronic liver disease had serum sodium measured. The HE was graded according to the West Haven classification [4 grades]. Relationship of hyponatremia was correlated with severity grade of encephalopathy using Spearman rank correlation test. Out of 202 patients, 62 [30.7%] patients had serum sodium less than 130 meq/l. Out of 202, HE was present in 69 [34.15%] patients and out of these, 38 had grade III-IV HE and 31 had grade I - II HE. Out of 69 patients with HE 57 had sodium less than 135 [p < 0.001]. Hyponatremia was a common feature in patients with cirrhosis and its severity increased with the severity of liver disease. The existence of serum sodium concentration < 135 mmol/L was associated with greater frequency of hepatic encephalopathy compared with patients with serum sodium concentration > 135 mmol/L

Effect of hepatitis B vaccination in patients with chronic hepatitis C

Objective: To assess the effects of hepatitis B vaccination on the antibody titer in patients with chronic hepatitis C and to compare it with response in normal healthy subjects. Study Design: Interventional study. Place and Duration of Study: Shifa International Hospital, Islamabad, Pakistan, from January 2007 to January 2012

Methodology: Hepatitis vaccination [Heberbiovac-HB 20] was given intramuscularly to the patients of chronic hepatitis C [HCV group] and normal healthy subjects [control group] at 0, 1 and 6 months intervals. Anti-HBs titer was determined after second and third injection to assess the antibody response

Results: There were 46 patients in the HCV group and 45 patients in the control group. Mean age was 40.9 +/- 9.8 years in the HCV group and 33.18 +/- 8.35 years in the control group. Weight was 67.04 +/- 13.5 kg in the HCV group and 71.78 +/- 14.63 kg in the control group. Height was 162.45 +/- 9.06 cm in the HCV group and 167.03 +/- 7.83 cm in the control group. Anti-HBs antibody levels after the second injection were 253.89 +/- 76.76 mlU/mL in the HCV group and 245.81 +/- 72.65 mlU/mL in the control group [p=0.172]. After third injection, the antibody levels were slightly higher in both groups

Conclusion: In patients with chronic hepatitis C and normal healthy subjects, Heberbiovac HB in standard dosage gave sero-protective levels in both groups and antibody titers were not significantly different in control and HCV group

Hepatocellular carcinoma after sustained viral response of interferon and ribavirin therapy in cirrhosis secondary to chronic hepatitis C

To determine the frequency of development of hepatocellular carcinoma in patients with chronic liver diseases secondary to hepatitis C who had achieved sustained virological response with Interferon and Ribavirin therapy. Retrospective descriptive study. Shifa International Hospital, Islamabad, Pakistan, from January 2007 to January 2012. Hepatitis C related chronic liver disease patients who were treated with interferon and ribavirin, after they achieved sustained virological response, they were followed for a mean of 42 +/- 17 months. During this time, development of hepatocellular carcinoma was ascertained. All underwent surveillance with alpha-feto-protein and ultrasonography every 6 months. Out of the 58 patients who had achieved sustained virological response, 3 developed hepatocellular carcinoma after a mean follow-up of 38 +/- 14 months. It was multifocal in 2 cases and was single lesion in the 3rd. Two patients ultimately died, one with upper GI bleeding and the other with hepatic encephalopathy, while 3rd patient with single lesion is still surviving. Three out of 58 patients of hepatitis C related chronic liver disease developed hepatocellular carcinoma during follow-up in patients who had achieved sustained virological response. These patients need closer follow-up, for development of complications, even if they have achieved sustained viral response

Factors affecting patient satisfaction during endoscopic procedures

To assess the quality and patient satisfaction in Endoscopy Unit of Shifa International Hospital. Cross-sectional survey. Division of Gastroenterology, Shifa International Hospital, Islamabad, Pakistan, from July 2011 to January 2012. Quality and patient satisfaction after the endoscopic procedure was assessed using a modified GHAA-9 questionnaire. Data was analyzed using SPSS version 16. A total of 1028 patients were included with a mean age of 45 +/- 14.21 years. Out of all the procedures, 670 [65.17%] were gastroscopies, 181 [17.60%] were flexible sigmoidoscopies and 177 [17.21%] were colonoscopies. The maximum unsatisfactory responses were on the waiting time before the procedure [13.13%], followed by unsatisfactory explanation of the procedure and answers to questions [7.58%]. Overall, unsatisfied impression was 4.86%. The problem rate was 6.22%.The quality of procedures and level of satisfaction of patients undergoing a gastroscopy or colonoscopy was generally good. The factors that influence the satisfaction of these patients are related to communication between doctor and patient, doctor's manner and waiting time for the procedure. Feedback information in an endoscopy unit may be useful in improving standards, including the performance of endoscopists.

Treatment of decompensated cirrhosis secondary to hepatitis c with antiviral therapy

To treat decompensated hepatitis C patient with interferon, ribavirin and amantidine to ascertain the sustained viral response. Descriptive study. Shifa International Hospital, Islamabad, from January 2007 to January 2012. HCV PCR patients with decompensated hepatitis C, who had developed a complication like ascites, encephalopathy or variceal bleeding were included in the study. Those with uncontrolled ascites or other complications were excluded. Treatment with standard interferon 3 miU subcutaneously three times a week along with ribavirin 800 mg to 1200 mg and amantidine 100 mg b.i.d. was administered for 12 months. Patients were followed every month with CBC and ALT and HCV PCR was performed after 3 months to document early viral response. They had HCV PCR at the end of the treatment to document end of treatment response. All were further followed for another 6 months at monthly intervals and HCV PCR was performed at the end of this period to document sustained viral response. In all, 165 patients were treated. Treatment had to be discontinued in 42 [26%] patients. Out of these, 16 patients died. Thus, 123 completed treatment. Sustained viral response was documented in 58 out of the 123 [47%] patients. Hepatic encephalopathy, gastrointestinal bleeding, sepsis and development of ascites were the major complications during treatment. Forty seven percent of patients with decompensated hepatitis C cirrhosis were able to achieve sustained viral response after one year treatment with anti-viral therapy. However, complications developed during treatment and, therefore, frequent and close monitoring is necessary in these patients.

long-term profile of patients with irritable bowel syndrome

To evaluate the symptom profile, course and prognosis of patients with irritable bowel syndrome [IBS] over a 15 years period. An observational study. Shifa International Hospital, Islamabad, Pakistan, from 1996 to 2011. Patients diagnosed with IBS at the study centre were followed for their clinical features, course over the period of time, management and its results. Only those patients were included in the study who completed the follow-up period. A total of 292 patients with mean age of 40.44 +/- 13.69 years were inducted. There were 156 [53.4%] males and 136 [46.6%] females. Nearly all male and female patients had abdominal pain and bloating. However, constipation was seen in 79.4% females and 71.6 males. Diarrhea was seen in 46.5% females and 42.7% males. Both constipation and diarrhea were seen in 27.3% female and 15.6% males. A high number of patients had concomitant illnesses and a large proportion of them had sleep disturbances, exacerbations with stress and had food sensitivities. This longitudinal follow-up study showed that, in our setting, there were more males suffering from this illness; females had more constipation-dominant features. Prognosis over the course of illness was excellent in all patients

Acute liver failure: an update

Acute liver failure is a serious medical emergency resulting from various insults that liver sustains. In our setting, viral etiology is the commonest cause. The syndrome results in significant liver damage leading to hepatic encephalopathy, coagulopathy and several other serious clinical consequences. Sepsis, cardio vascular failure and renal failure can result in multi system organ failure and fatal consequences. Management requires identification of etiologic agent as soon as possible. Nursing care in intensive care unit [ICU] setting is recommended. Attention towards correction of electrolyte imbalance, coagulopathy, encephalopathy and systemic complication along with judicious use of antibiotics help in obtaining a favorable outcome. Transplant remains the ultimate management

Severity of depression in hepatitis B and hepatitis C patients

To assess and compare the severity of depression in chronic hepatitis B [CHB], chronic hepatitis C [CHC] and healthy subjects. Comparative study. Shifa International Hospital, Islamabad from July 2011 to February 2012. A total of 206 subjects were divided in three groups. Group-I [chronic hepatitis C, n = 95], group-II [chronic hepatitis B, n = 29] and group-III [healthy subjects, n = 82]. They were matched for age, gender and socioeconomic status and were compared for frequency and severity of depression as measured by Hospital Anxiety and Depression Scale [HADS]. Some degree of depression was noted in all groups. Frequency of depression was 72.6% in group-I, 58.6% in group-II and 37.8% in group-III [p value < 0.001]. Both CHC and CHB had high frequency of some degree of depression. Hepatitis C patients had more depressive features than CHB. It is worthwhile to do more close mental health observation in them. A multidisciplinary team including a psychiatric specialist can help in this approach

Emerging therapies in irritable bowel syndrome

To determine with the mechanism of action involved in the therapeutic potential of serotonin and its blocker on gastrointestinal motility. The standard method was used for obtaining the longitudinal and circular muscles strip of rabbit ileum for in vitro studies. Each muscle strip was exposed to serotonin and its blocker and the result obtained was recorded on polygraph apparatus. The effects were recorded in vice versa fashion i.e. agonist v/s antagonist and antagonist v/s agonist on longitudinal and circular muscle strip separately. Serotonin had depressant effect on the force of contraction. On addition of antagonist in the presence of agonist, the effects were increased. Longitudinal muscle showed more pronounced effect i.e. 52.7% with methysergide in comparison to circular muscle, which was 15.6%. Circular muscle showed reduction in the force of contraction with serotonin, which was increased on addition of antagonist, but still below the level of base line contraction. Serotonin when given from external source in vitro, decreased the force, however, there was minimal increase in the rate of contraction. Hence, serotonin decreases the intestinal motility giving an impression of having antispasmodic effect. The results of this study can be utilized in the development of new drug related to G.I. motility mediated through 5HT receptors