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 [DHandMC]. 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 SVR[12]. Chi square Chi[2] 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 SVR[12], 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] SVR[12] 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

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

Hep-net opinion about the management of patients with chronic hepatitis C in Pakistan in the era of available direct acting antivirals

In Pakistan, we have 4.9% prevalence of HCV in general population, with 79% genotype 3. Recently Sofosbuvir has been made available at compassionate price in Pakistan. Management of chronic hepatitis C includes counseling of HCV patients, their proper assessment to select those who need antiviral therapy, initiation of appropriate antiviral agents and duration of therapy, along-with careful monitoring for safety and efficacy. Hepatic status as well as previous history of HCV therapy needs to be taken in the consideration before starting antiviral therapy. Other factors include co-morbid conditions like obesity, DM, NASH, etc. Treatment of special populations like liver transplant patients, patients with HBV co-infection, chronic kidney disease and hemoglobinopathies need special considerations when initiating HCV therapy

Predicting prognosis in hepatocellular carcinoma: comparison of staging systems in Pakistani cohort

To determine the clinical, biochemical and radiological prognostic indicators and to compare the performance of six staging systems in patients of hepatocellular carcinoma [HCC]. Descriptive study. Department of Gastroenterology, Doctors Hospital, Lahore, from October 2007 to December 2013. 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. 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. 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

Response guided interferon therapy for genotype 3 of chronic hepatitis C: compliance and outcome

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. 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. 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]. 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

Frequency of depression and somatic symptoms in patients on interferon alpha/ribavirin for chronic Hepatitis C

Large numbers of patients suffering from Chronic Hepatitis C [HCV] are seeking treatment with interferon alpha [IFN] because of significant advances in overall improvement in the course of HCV and its complications. Objectives were to estimate the frequency of depression and somatic symptoms in patients on interferon alpha/ribavirin treatment for chronic hepatitis C. It was an observational study conducted in the out-patient Department of Gastroenterology Shaikh Zayed Hospital, Lahore during a period of three months, i.e., from September to November 2008. One hundred consecutive patients undergoing interferon alpha/ribavirin treatment for chronic HCV were included in the study. All patients, irrespective of age, sex or duration of treatment were administered with a check list of common physical complaints and DSM-IV symptoms for Major Depressive Episode. Out of a total of 100 subjects 37 were male and 63 were female. In all, 39 [39%] patients fulfilled the diagnostic criteria of DSMIV for Major Depressive Episode. Major Depression was more common in female 28 [44.4%] as compared to male 11 [28.7%] patients. Somatic symptoms were common in all the patients but they were reported more frequently by patients with Major Depression compared to those without Major Depression. Myalgias, headache, joint pain, nausea/vomiting, abdominal pain and palpitation were the most common physical symptoms. Major Depression and somatic complaints are a common consequence of interferon alpha/ribavirin treatment for chronic hepatitis C. All patients receiving this treatment should be periodically assessed for the detection of these side effects to promptly address relevant treatment options

Efficacy of argon plasma coagulation in gastric vascular ectasia in patients with liver cirrhosis

To determine the efficacy of Argon Plasma Coagulation [APC] in terms of improvement in hemoglobin level and disappearance of telangiectasia as endoscopic treatment for Gastric Antral Vascular Ectasia [GAVE] and Diffuse Antral Vascular Ectasia [DAVE] syndrome in liver cirrhosis. Quasi experimental study. Department of Gastroenterology and Hepatology of Shaikh Zayed Hospital/ Federal Postgraduate Medical Institute, Lahore, from January, 2006 to July, 2007. Cirrhotic patient with gastric vascular ectasia were enrolled and followed-up for 18 months with repeated sessions of APC. Efficacy of APC was evaluated on the basis of patient's symptoms, transfusion requirements and hemoglobin levels. APC was performed by using ERBE generator set at 60 W and flow rate 2.0 L/min using primarily endfiring probes. Fifty patients were enrolled in the study. Mean age was 55.78+1.24 years with 32 males and 18 females giving a male to female ratio 1.7:1. Forty two patients were in Child's Class C and 8 in Child's Class B. Presenting complaints were malena and anemia. Two hundred and fifty three APC sessions were carried out; mean 5.06 + 1.5 sessions per patient. Mean follow-up period after the last session was 8.5 + 3.7 months. Mean increase in the hemoglobin level was 1.35 + 0.24 g/dl. There was no death of any patient during the study period. Treatment with APC is an effective and safe method to decrease blood loss in patients with GAVE and DAVE

Propranolol, isosorbide mononitrate and endoscopic band ligation - alone or in varying combinations for the prevention of esophageal variceal rebleeding

To compare the efficacy of propranolol, propranolol with nitrate, band ligation, and band ligation with propranolol and nitrate for the prevention of esophageal variceal rebleeding. A prospective randomized trial. Department of Gastroenterology and Hepatology, Sheikh Zayed Hospital, Lahore, from November 2003 to July 2005. One hundred and sixty cirrhotic patients with esophageal variceal bleeding were randomized to four treatment groups [propranolol, propranolol plus isosorbide mononitrate, band ligation, band ligation plus propranolol and nitrate] with 40 patients in each group. Patients were followed for 6 months after the enrolment of last patient. Primary end points were recurrence of esophageal variceal bleeding and death. Treatment complications were noted. Four treatment groups were comparable regarding baseline characteristics. Esophageal variceal rebleeding occurred in 22% patients in band ligation plus drugs group, 26% patients in drug combination group, 31% patients in banding group and 38% patients in propranolol group [p=0.41]. Difference in mortality rates was also not significant. There was no significant difference between treatment groups in prevention of esophageal variceal rebleeding

Thrombotic thrombocytopenic purpura, at a tertiary care centre in lahore, Pakistan

Thrombotic thrombocytopenic purpura is a syndrome, characterized by microangiopathic hae-molytic anaemia, thrombocytopaenia, neurological symptoms, renal disease and fever. Commonly considered rare, but actually it is one of the most under diagnosed disorders. This study was aimed at evaluating the clinical features, course, prognostic factors and treatment outcome in 17 patients diagnosed as having thrombotic thrombocytopaenic purpura [TTP]. It was a cross-sectional descriptive study at Shaikh Zayed Hospital Lahore. This study includes patients diagnosed as having TTP by the department of haematology from January 2005 to December 2007. Eight of 17 patients were treated with plasma exchange. Six of these 8 patients survived. Plasma infusions were performed in 9 patiejits, 5 of them recovered. Overall 65% patients recovered and mortality was 35%

Successful treatment of watermelon stomach / GAVE syndrome by using argon plasma coagulation

This case report describes a 50-year-old female patient with liver cirrhosis presented with anemia. She was found to be suffering from gastric antral vascular ectasia [watermelon stomach] on upper gastrointestinal endoscopy. She underwent multiple sessions with Argon plasma coagulation, a non-contact thermal method of hemostasis for the management of watermelon stomach. After 3 sessions, the lesions disappeared and the hemoglobin increased by 2.4 gm/dl without any need of transfusion

Frequency of hepatopulmonary syndrome in cirrhotic patients

To determine the frequency of Hepatopulmonary Syndrome [HPS] in patients with cirrhosis of the liver. Observational cross-sectional study. Department of Gastroenterology and Hepatology, Shaikh Zayed Hospital, Lahore, from April 2005 to March 2006. Fifty consecutive patients admitted with liver cirrhosis were recruited. Twelve patients were excluded due to inadequate echocardiography image quality and inability to perform lung function tests. The diagnosis of cirrhosis was made on clinical, biochemical, serological and metabolic workup, ultrasound abdomen or liver biopsy. Complete blood count, liver function tests, prothrombin time, serum albumin, electrocardiography, chest radiograph, transthoracic contrast echocardiography, arterial blood gas analysis and pulmonary function tests [FEV1] were performed. Results were analyzed as percentages. Chi-square test of proportions and t-test were applied. Total patients evaluated were 38. Mean age was 47.92 +/- 11.38 years, with male [68.4%] to female [31.6%] ratio of 2.1:1. The commonest cause of cirrhosis was hepatitis C [71.1%]. Out of the 38 patients, 11 [28.9%] had HPS including 5 [13.2%] with overt HPS and 6 [15.8%] with subclinical HPS. All patients with HPS had hepatitis C with Child-Pugh- Turcotte [CPT] class C. Factors associated with HPS were digital clubbing, arterial hypoxemia and intrapulmonary vascular dilatations [p=0.02, 0.05 and 0.000 respectively]. In this study, 28.9% patients with cirrhosis of the liver had HPS. All belonged to child class C due to hepatitis C. Digital Clubbing, arterial hypoxemia and intrapulmonary vascular dilatations were important features of hepatopulmonary syndrome

Effect of band ligation on portal hypertensive gastropathy and development of fundal varices

Use of endoscopic therapies for esophageal varices has resulted in increased prevalence of fundal varices and severe portal hypertensive gastropathy. This study was meant to compare the effect of band ligation and sclerotherapy on development of fundal varices and portal hypertensive gastropathy. Patients with esophageal varices presenting in the endoscopy unit of Shiakh Zayed Hospital, with at least one previous endoscopy were included. Patient's past record was reviewed for findings and type of treatment given for varices during first endoscopy, number of endoscopies till date, number of esophageal varices band ligation [EVBL] or sclerotherapy sessions. All patients underwent upper GI endoscopy and findings were recorded. Type of treatment patient rendered during first endoscopy either EVBL or sclerotherapy was correlated to the presence of fundal varices and severity of portal hypertensive gastropathy observed on present endoscopy, using Chi square test [chi [2]]. Eighty one patients were included. Mean age of patients was 48.7 +/- 12.63. Esophageal varices band ligation was carried out during first endoscopy in 49 [60.5%] patients and sclerotherapy in 31 [38.2%] patients. On fresh endoscopy, fundal varices were seen in 25 [30.8%] patients. Severe portal hypertensive gastropathy was found in 26 [32.1%] and mild in 54 [66.7%] patients. Severity of portal hypertensive gastropathy and presence of fundal varices in recent endoscopy was significantly more in patients with EVBL in first endoscopy. Band ligation of esophageal varices is associated with more frequent development of fundal varices and worsening of portal hypertensive gastropathy compared to sclerotherapy

Serum alanine aminotransferase level and response to interferon ribavirin combination therapy in patients with chronic hepatitis c

To determine the difference in sustained virological response to interferon-ribavirin combination therapy between patients with normal ALT and those with raised ALT in chronic hepatitis C. Quasi-experimental study. Department of Gastroenterology and Hepatology, Shaikh Zayed Postgraduate Medical Institute, Lahore, from February 2004 to June 2005. Patients with positive HCV RNA by PCR and compensated liver disease were included and divided in two groups. One group with ALT below upper normal limit [UNL= 65U/L] and second group with raised ALT [> 1x UNL]. After treatment with standard interferon alpha 2a and ribavirin, both groups were checked for sustained viral response [SVR] six months after end of treatment and compared for response to therapy with Chi square test. Of the 70 patients included, 25 had normal ALT [<1 x upper normal limit UNL] and 45 had ALT above upper normal limit [> 1 x UNL]. Of these, 63 patients completed treatment. Sustained viral response [SVR] was seen in 13 of 22 patients with normal ALT who completed therapy and 22 of 41 patients with raised ALT who completed treatment. Difference in SVR in two groups was not significant [p 0.679]. When patients with raised ALT were sub-classified, significantly better response was seen in patients with ALT 2 times the upper normal limit [p 0.021]. Patients with normal baseline ALT respond equally well to combination therapy as is seen in patients with raised ALT

Frequency of Hepatitis B, C and Human Immunodeficiency virus in blood donors at Shaikh Zayed Hospital, Lahore

To find out the frequency of hepatitis B, C and human immunodeficiency virus [HIV] in blood donors at Shaikh Zayed Hospital, Lahore. Design: This is a non-interventional study. Study Period: Period of this study is from 1-1-2005 to 30-6-2005. Study was conducted at the Blood Bank of Shaikh Zayed Hospital, Lahore. Subjects and Methods: In this study 18216 young healthy voluntary blood donors [age 16-50 years] comprising of 16611 males and 1605 females were included and tested for HBsAg, Anti-HCV and HIV by Accu check one step test [chromatographic immunoassay] in serum. Results: Frequency of hepatitis B, C and HIV infection was 3.36%, 4.16% and 0% respectively. We can get representative prevalence values of HBV, HCV and HIV infection in general population by collecting data from all blood transfusion centers of Pakistan. This is also helpful to create public awareness regarding hepatitis and HIV transmission through blood transfusion

Value of Quantitative HCV RNA in management of Chronic Hepatitis C patients with genotype 2 and 3

Determination of viral load by quantitative polymerase chain reaction [PCR] for hepatitis C virus [HCV] is part of workup before initiating interferon and ribavirin combination therapy for chronic hepatitis C. This study was carried out to determine predictive value of baseline viral load in patients with viral genotype 2 and 3, for response to therapy. Patients with chronic hepatitis C and genotype 2 and 3 were included in study. Viral load was determined before starting treatment with standard interferon and ribavirin for six months in all patients. Patients were checked for cod of treatment [EOT] and sustained viral response [SVR] by qualitative PCR for HCV. Response to therapy was correlated with baseline viral load by student`s t test. Total of 55 patients were included. Male to female ratio was 1.1/1 [29/26]. Six patients were of genotype 2, one patient was harboring both genotype 2 and 3 while rest of 48 patients had genotype 3 of hepatitis C virus. Baseline viral load was less than 2 million copies/ml in 25 patients while 30 patients had viral load in excess of 2 millions copies/ml. Treatment was completed in 50 patients. Sustained viral response [SVR] was seen in 31 patients and 19 patients were non-responders. No significant association was found between response to therapy and baseline viral load. Pre-treatment viral load is not predictive of response to combination therapy with interferon in patients with genotype 2 and 3

Non-endoscopic prediction of presence of esophageal varices in cirrhosis

To identify hematological, biochemical and ultrasonographic predictors of esophageal varices in patients of cirrhosis. Cross-sectional, analytical study. Department of Gastroenterology, Shaikh Zayed Postgraduate Medical Institute, Lahore, from September 2003 to March 2004. One hundred and one patients with established cirrhosis and no history of variceal bleed underwent physical examination, hematological, biochemical tests and abdominal ultrasound examination. Esophagogastroduodenoscopy [EGD] was carried out in all patients. Presence of varices on EGD was correlated with hematological, biochemical and ultrasonographic variables by regression analysis. Esophageal varices were seen in 65 patients while 36 patients had no varices. High grade varices were seen in 15 patients and 50 patients had low grade varices. Serum albumin less than 2.95g/dl, platelet count less than 88 x 10[3]/micro L and portal vein diameter more than 11mm were associated with presence of varices. High grade varices were predicted by serum albumin < 2.95g/dl and portal vein diameter more than 11mm. Patients with serum albumin < 2.95g/dl, platelet count < 88 x 103/mL and portal vein diameter > 11mm are more likely to have high grade varices. These patients are candidates for surveillance endoscopy

Ectopic intestinal varices as a rare cause of lower gastrointestinal haemorrhage

Ectopic intestinal varices are rarely responsible for lower gastrointestinal [GI] haemorrhage. A case of 55 years old male with recurrent melena is being presented, who was found to have scattered varices on small as well as large intestine. Selective review of literature regarding presentation, diagnosis and management of these cases is also part of presentation

Pattern of hepatitis delta virus infection in the Shaikh Zayed hospital, Lahore

Hepatitis delta virus [HDV] is a hepatotropic virus. It infects only in the presence of hepatitis B virus [HBV]. HBV infection in Pakistan is high; the infection with the delta virus, therefore, goes hand in hand with HBV infection. HDV coinfects in the presence of HBV or superinfects a carrier of HBsAg. Superinfection by HDV is generally more severe than HBV infection alone. Therefore, the purpose of this study was to evaluate the frequency of HDV in our patient population. Sera of 150 HBsAg positive patients were tested for anti-HDV. Twenty-five [16.67%] were found positive. Sera of these 25 patients were further tested for HBc-IgM antibodies. Six were found positive, indicating 24% of coinfection and 67% superinfection by delta virus. In as much as almost 17% of HBV infection had associated delta virus infection with reported high complications of fulminant hepatitis and chronicity, it is recommended that vaccination against HBV must be adopted as a universal policy

Comparison of ultrasonography and cholangiography [ERCPL/PTC] differential diagnosis of obstructive jaundice

Diagnostic accuracy of ultrasonography and cholangiography [ERCP/PTC] was compared in determining the site and nature of obstruction in obstructive jaundice. Ultrasound was performed in 50 patients with clinical diagnosis of obstructive jaundice. All patients subsequently underwent ERCP/PTC and/or surgery. ERCP was performed in 38 and PTC in 15 patients. The positive predictive value for the site and etiology of obstruction by ultrasonography was 94% and 86% respectively. In comparison, the cholangiography [ERCP/PTC] had positive predictive value of 100% in site and 98% in etiology. High degree of accuracy and non-invasiveness makes ultrasound as the primary radiological tool in the differential diagnosis of obstructive jaundice. ERCP is the gold standard for determining the precise level and cause of obstruction. PTC adds further to ultrasound based diagnosis of obstructive jaundice particularly in proximal obstruction and in ERCP failure

Endemic transmission of hepatitis C

The mode of transmission in hepatitis C related chronic liver disease and liver cirrhosis was studied in 144 patients. A careful history [hx] of blood transfusion [BT], needle stick from non-disposable needle [NS], surgery [S], and close contact with hepatitis C [contact] patient was taken in all cases. Thirty five patients had hx. of BT, 72 had NS, none had S, and 5 had hx, of contact. Thirty seven [25.69%] did not have any hx- of apparent reason of transmission of Hepatitis C known as community based or endemic cases