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INTRODUCTION. Patients with advanced liver disease and cirrhosis secondary to viral diseases have a tendency to develop serious complications of cirrhosis.
ORIGINAL ARTICLE

Treatment of Decompensated Cirrhosis Secondary to Hepatitis C with Antiviral Therapy Nasir Khokhar1,2, Muhammad Omar Qureshi1 and Tariq Khan Niazi2

ABSTRACT

Objective: To treat decompensated hepatitis C patient with interferon, ribavirin and amantidine to ascertain the sustained viral response. Study Design: Descriptive study. Place and Duration of Study: Shifa International Hospital, Islamabad, from January 2007 to January 2012. Methodology: 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. Results: 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. Conclusion: 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. Key Words: Hepatitis C. Cirrhosis. Chronic liver disease. Interferon. Ribavirin. Amantidine.

INTRODUCTION

Patients with advanced liver disease and cirrhosis secondary to viral diseases have a tendency to develop serious complications of cirrhosis. In Pakistan, hepatitis C (HCV) is a frequent illness and results in decompensation and development of serious complications, which include ascites, esophageal variceal bleeding, hepatic encephalopathy and hepatocellular carcinoma.1 The course of hepatitis is progressive in these patients and as they reach cirrhotic state, they develop decompensation and their lifespan is limited. Antiviral therapy is commonly not recommended in patients with cirrhosis with signs of decompensation, as they may not tolerate therapy.2 However, the majority of cirrhotics with HCV infection have reasonably stable hepatic function and after a successful treatment of a decompensating event, they might be suitable candidates for antiviral therapy. Tolerance to antiviral therapy by these patients may be extremely poor due to their advanced disease. Department of Gastroenterology1 / Medicine2, Shifa International Hospital, Islamabad. Correspondence: Dr. Nasir Khokhar, House No. 13, Street 44, F-8/1, Islamabad. E-mail: [email protected] Received: November 19, 2012; Accepted: August 16, 2013.

However, the only option for them is antiviral treatment, in an attempt to eradicate the virus and to arrest the disease at a stage where they suffer fewer decompensating events and can have prolonged survival. Several studies have been performed in various parts of the world in this subset of patients where standard and Pegylated interferon both have been used.3-8 In these studies, sustained virologic response (SVR) has varied from 20 to 58%. The treatment in these patients is especially desirable as cirrhosis has some reversibility.9 There are other encouraging reports showing that in patients achieving SVR, there is marked reduction in liver related morbidity and mortality.3,4,6 They tolerated therapy reasonably well also.5,8 The aim of this study was to analyze the use of standard interferon, ribavirin and amantidine in patients with decompensated cirrhosis in an attempt to eradicate the virus.

METHODOLOGY

The study was carried out at the Department of Gastroenterology at Shifa International Hospital, Islamabad, Pakistan, from January 2007 to January 2012. An informed consent was obtained from all patients prior to initiation of treatment. Patients with chronic liver disease (CLD) secondary to hepatitis C, who had one or more

Journal of the College of Physicians and Surgeons Pakistan 2013, Vol. 23 (12): 833-836

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Nasir Khokhar, Muhammad Omar Qureshi and Tariq Khan Niazi

complications like ascites, hepatic encephalopathy or episode of variceal bleeding were included in the study after an informed consent. Those patients who had variceal bleeding underwent upper GI endoscopy and esophageal band ligation was performed and prophylaxis with propranolol was instituted. Those who had ascites, were managed with dietary restriction and diuretics and when it was optimally controlled, the treatment was instituted. Patients with uncontrolled ascites, recurrent bleeding, or recurrent hepatic encephalopathy were excluded from the analysis. Diagnosis of CLD was based on clinical, laboratory and ultrasonological features.

Standard interferon alpha-2b 3 miU subcutaneously was administered along with ribavirin 800 – 1200 mg, and amantadine 100 mg b.i.d orally. Other supportive treatment like diuretics, lactulose, propranolol and proton pump inhibitors (PPIs) were continued, as needed. The patients were followed every month with CBC and HCV PCR was performed at 3 months to document early viral response (EVR). Subsequently, they were followed every month with CBC and ALT. HCV PCR was performed at the end of treatment, which was 12 months (ETR). After that, they were followed every month and standard treatment for CLD was continued and HCV PCR was performed at the end of 6 months to document SVR. Those patients who became HCV PCR positive during this period were labeled as relapsers. The data was collected in a well custom designed proforma and analyzed using Statistical Package for Social Sciences (SPSS) version 16. Frequency and percentage of different variables were determined. Clinical data were presented as mean and standard deviation. Student t-test, chi-square and Fisher exact test applied where applicable. P-value less than 0.05 was considered statistically significant.

RESULTS

Out of 165 patients, 120 were males and 45 were females. The mean age was 45 ± 16 years. The demographic characteristics of patients are shown in Table I.

In 42 (26%) patients, treatment had to be terminated for various reasons. Out of these 42 patients, 16 died (Table II). A total of 123 patients completed the treatment. Twentyeight (23%) were non-responders. Out of 123 patients, 95 (77%) achieved ETR. Out of these, 58 (47%) achieved SVR, while 37 (30%) patients relapsed (Figure 1).

Outcome analysis showed that patients in child class C were those in whom treatment had to be stopped and some died of complications (Table III).

Those patients who died, predictors of mortality were analyzed. Older age, higher serum bilirubin, higher CPT score and MELD score were found to be factors affecting mortality (Table IV). 834

Figure 1: Outcome of treated patients.

Table I: Demographic characteristics of study population (n = 165). CPT Class A

CPT Class B

CPT Class C

Total bilirubin (mg/dl)

1.0 ± 0.4

1.8 ± 0.6

2.7 ± 0.8

Prothrombin time (sec)

14.2 ± 1.7

16.3 ± 0.8

17.1 ± 0.2

Haemoglobin (g/dl)

11.7 ± 1.2

11.2 ± 1.1

10.8 ± 1.4

65 ± 12

59 ± 13

Number (%)

78 (47)

Baseline Laboratory values Albumin (g/dl)

3.1 ± 0.3

Leukocytes/microlitre

4.2 ± 0.4

Platelets/microlitre

90 ± 35

ALT (u/l)

CPT score

5±1

55 (33)

2.9 ± 0.3

3.9 ± 0.3 75 ± 21

32 (20)

2.6 ± 0.4

3.7 ± 0.2 68 ± 18 68 ± 14

7 ± 1.1

9.7 ± 1.3

Table II: Reasons for termination of treatment and mortality (n = 42). Complication

Hepatic encephalopathy

Number developed (%)

Gastro-intestinal bleeding Worsening ascites Sepsis

18 (43)

Number died (%)

9 (21)

6 (37)

8 (19)

00

2 (5)

00

2 (5)

Thrombocytopenia

Psychosis

1 (6.25)

3 (7)

Total

9 (56)

00

42 (100)

16 (100)

Table III: Outcomes in patients with different child classes. Outcome

Non-responder

Child class A Child class B Child class C (n=78)

15 (19.2%)

(n=55)

8 (14.5%)

Sustained response

28 (35.8%)

19 (34.5%)

Relapsed

18 (23.07%)

12 (21.8%)

Treatment stoppage 17 (21.79%) 16 (29.09%) Mortality

3 (3.84%)

5 (9.09%)

Total

p-value

(n=32)

(n=165)

11 (34.3%)

58

0.93

7 (21.8%)

37

0.98

5 (15.6%)

9 (28.12%) 8 (25%)

28

42

16

0.75 0.59