Appraisal of a newly developed ALBI-sarcopenia score as a prognostic marker in patients with hepatocellular carcinoma.

OBJECTIVE: This study aimed to evaluate the impact of the combined Albumin-bilirubin (ALBI)/sarcopenia score as a newly developed prognostic model for hepatocellular carcinoma (HCC), with a focus on its utility in predicting mortality. METHODS: This prospective study was conducted on HCC patients who were followed for 1 year or until death. Sarcopenia was assessed radiologically by computed tomography at the level of L3. The study consisted of two sets: a development set in which the new ALBI-sarcopenia score was created, comprising 262 HCC patients, followed by an internal validation set with 100 patients. RESULTS: The development cohort primarily included males (69.5%), aged 59.6 ± 8.09 years. In patients with sarcopenia, the ALBI score was -2.03 ± 0.42 ( P < 0.006), the model for end-stage liver disease (MELD) score was 11.29 ± 2.43 ( P < 0.001*), and the MELD-sarcopenia score was 21.29 ± 2.43 ( P < 0.001*). The distribution of barcelona clinic liver cancer (BCLC) staging was as follows: BCLC A 18 (15.9%), BCLC B 63 (55.8%) and BCLC C 32 (28.3%) ( P < 0.001*), with a notable association with higher mortality ( P < 0.001). Multivariate analysis identified sarcopenia and ALBI scores as independent predictors of mortality in HCC ( P < 0.001*). In the development set, the ALBI-sarcopenia score successfully predicted mortality at a cutoff >-11 with an area under a curve of 0.837 (95% CI, 0.784-0.889), while in the validation set, it predicted mortality at a cutoff >-11.55 with an area under a curve of 0.842 (95% CI, 0.753-0.930). CONCLUSION: The newly introduced ALBI-sarcopenia score has demonstrated superior effectiveness in comparison to MELD-sarcopenia score, overcoming the shortcomings associated MELD score in forecasting outcomes for patients with HCC.

Impacts of rifaximin and midodrine on morbidity, mortality, and quality of life in patients with decompensated liver cirrhosis.

BACKGROUND: Vasodilatation and bacterial dislocation are the main contributors to the catastrophic events in patients with decompensated liver cirrhosis (DLC). AIM: The aim of this study was to evaluate the impacts of adding midodrine and rifaximin on morbidity, mortality, and quality of life in patients with DLC. METHODS: This interventional clinical study included 100 consecutively enrolled DLC patients randomized 1 : 1 into two groups. Group A received oral midodrine (5 mg/8 h) and rifaximin (550 mg/12 h) with standard diuretic therapy, while group B received only standard diuretic therapy. Clinical and laboratory data, including the McGill Quality of Life Questionnaire, were evaluated over a 3-month treatment period. RESULTS: In the study group, there was a significant reduction in Child-Pugh and Model for End-Stage Liver Disease scores, international normalized ratio, and mean arterial blood pressure at 2, 6, and 12 weeks (P < 0.05). Ascites, spontaneous bacterial peritonitis incidence, hematemesis, paracentesis need, and hepatic encephalopathy showed improvement after 12 weeks compared with the control group. McGill Quality of Life Questionnaire significantly improved after 6 and 12 weeks (P < 0.05). Survival rates demonstrated a noteworthy improvement (P = 0.014), substantiated by evidence in both univariate and multivariate regression analyses. CONCLUSION: Combined midodrine with rifaximin represents an endowment to patients with DLC with spectacular improvements in synthetic liver functions, along with improved quality of life, and survival.

Liver transplantation for hepatocellular carcinoma: a model including α-fetoprotein improves the performance of Milan criteria.

BACKGROUND & AIMS: The aim of this study was to generate an improved prognostic model for predicting recurrence in liver transplant candidates with hepatocellular carcinoma (HCC). METHODS: Predictors of recurrence were tested by a Cox model analysis in a training cohort of 537 patients transplanted for HCC. A prognostic score was developed and validated in a national cohort of 435 patients followed up prospectively. RESULTS: α-Fetoprotein (AFP) independently predicted tumor recurrence and correlated with vascular invasion and differentiation. At a Cox score threshold of 0.7 (area under the receiver operating characteristic curve, 0.701; 95% confidence interval, 0.63-0.76; accuracy, 75.8%), a model combining log(10) AFP, tumor size, and number was highly predictive of tumor recurrence and death. By using a simplified version of the model, with untransformed AFP values, a cut-off value of 2 was identified. In the validation cohort, a score greater than 2 predicted a marked increase in 5-year risk of recurrence (50.6% ± 10.2% vs 8.8% ± 1.7%; P < .001) and decreased survival (47.5% ± 8.1% vs 67.8% ± 3.4%; P = .002) as compared with others. Among patients exceeding Milan criteria, a score of 2 or lower identified a subgroup of patients with AFP levels less than 100 ng/mL with a low 5-year risk of recurrence (14.4% ± 5.3% vs 47.6% ± 11.1%; P = .006). Among patients within Milan criteria, a score greater than 2 identified a subgroup of patients with AFP levels greater than 1000 ng/mL at high risk of recurrence (37.1% ± 8.9% vs 13.3% ± 2.0%; P < .001). Net reclassification improvement showed that predictability of the AFP model was superior to Milan criteria. CONCLUSIONS: Prediction of tumor recurrence is improved significantly by a model that incorporates AFP. We propose the adoption of new selection criteria for HCC transplant candidates, taking into account AFP.

Impact of intermittent fasting on laboratory, radiological, and anthropometric parameters in NAFLD patients.

Aim of the study: Despite the ample flow of non-alcoholic fatty liver disease (NAFLD) drugs in the pipeline, lifestyle modifications are still the optimal solution of NAFLD. The aim of the study was to assess short term effects of Ramadan fasting (RF) as a sort of intermittent fasting (IF) on biochemical, radiological, and anthropometric parameters of NAFLD patients. Material and methods: Ninety-eight NAFLD patients were recruited and voluntarily subjected to 16 hours daily fasting for an average of 22-29 days, without special dietary recommendations. Anthropometric, laboratory and radiological parameters were measured before, at 30 days, and one month after fasting (fasting and non-fasting phases). Results: Patients were mostly rural (76%), hypertensive (34.7%), diabetic (43.9%), and female (76.8%), with overt criteria of metabolic syndrome (67.3%). Liver transaminases (ALT and AST) were ameliorated significantly after fasting (p ≤ 0.01), which continued in the following month (p ≤ 0.01) especially in those with elevated ALT before fasting (46%). Eleven patients (24.4%) experienced ALT normalization after one month of fasting, which was further increased to 15 (33.3%) one month later. Lipid profiles (cholesterol, triglycerides, HDL, LDL, cholesterol/HDL risk ratio) were significantly corrected following IF (p ≤ 0.01) and continuing in the next phase (p ≤ 0.010). Body mass index (BMI) lessened following the fasting (p ≤ 0.01), while no remarkable changes were noted regarding waist, hip, and triceps skin fold thickness (p ≤ 0.01). Glycemic indices (HbA1c, postprandial, HOMA-IR) and fibrosis markers (FIB-4 and APRI) were significantly ameliorated (p ≤ 0.01), while reduction in inflammatory markers was not long lasting (p ≤ 0.01). Conclusions: Intermittent fasting led to momentous improvements in ultrasonographic, biochemical, and anthropometric parameters of NAFLD especially in early phases and prediabetics.

Survival of a case of pre-eclampsia complicated with acute fatty liver of pregnancy and acute pancreatitis.

Acute fatty liver of pregnancy (AFLP) and acute pancreatitis are peculiar complications of pregnancy. When acute pancreatitis occurs co-incidentally with acute fatty liver of pregnancy, mortality is high. Here, we report a case of a 22-year-old lady in her 36th week of gestation, who presented with pre-eclampsia, acute fatty liver of pregnancy and acute pancreatitis. She fulfilled six Swansea criteria for diagnosis of AFLP, and the diagnosis of acute pancreatitis was based on clinical suspicion, elevated pancreatic enzymes and the sonographic appearance of a swollen pancreatic head.

Impact of tumour differentiation to select patients before liver transplantation for hepatocellular carcinoma.

AIM: To generate a new score with improved accuracy compared with Milan criteria to select patients. PATIENTS: The training cohort comprised 373 patients transplanted for hepatocellular carcinoma (HCC) between 1988 and 1998 (cohort 1). An algorithm was derived from the analysis of patient data by the proportional hazard Cox regression model. The area under the receiver operating characteristic (AUROC) was used to determine a cut-off value. The validation cohort comprised 140 patients transplanted between 1999 and 2001 (cohort 2). RESULTS: Multivariate analysis identified three predictors of 5-year tumour-free survival: tumour differentiation (P=0.02), diameter (P<0.0001) and number of nodules (P=0.04). A cut-off value of 4 was derived from the AUROC of the final score. Five-year tumour-free survival was 60.2 ± 3.1% in patients with as score <4 and 36.4 ± 4.7% in individuals with a score ≥4, P<0.0001. In the validation cohort, 5-year tumour-free survival was 82.8 ± 3.6% (score <4) and 50.0 ± 10.7% (score ≥4), P=0.0003. In patients with a score <4, there was no significant difference in 5-year tumour-free survival between Milan+ and Milan- patients, either in cohort 1 or 2. Five-year tumour-free survival of Milan- patients was significantly better in individuals with a score <4 compared with those with a score ≥4, both in cohort 1 (61.5 ± 9.1 vs 31.4 ± 4.6%, P=0.009) and in cohort 2 (P=0.02). CONCLUSION: A novel score taking into account tumour differentiation shows higher accuracy than Milan criteria in predicting 5-year tumour-free survival following liver transplantation for HCC. Prospective studies should validate these findings.

MELD-Sarcopenia is Better than ALBI and MELD Score in Patients with Hepatocellular Carcinoma Awaiting Liver Transplantation.

BACKGROUND: The albumin bilirubin (ALBI) score and model of end stage liver disease (MELD) are prognostic in patients with hepatocellular carcinoma (HCC). Aim was to compare MELD-sarcopenia to MELD and ALBI scores in patients with HCC awaiting liver transplantation. METHODS: patients with HCC (n=262) were included and followed up for 12 months. Baseline MELD, ALBI and MELD-sarcopenia models were calculated. RESULTS: The average age was 59.61 ±8.09 years. Most patients were males (69.5%), CTP class A (55.7%) and BCLC stage B (54.2%). Hepatitis C virus was the main cause of liver cirrhosis in most patients (88.9%). The average MELD, MELD-sarcopenia and median ALBI score were 10.65 ±2.54, 15.11 ±6.22 and -2.12 (0.74) respectively. Sarcopenia patients had higher MELD, ALBI and MELD-sarcopenia values. Patients with sarcopenia had lower survival (10.09 months) than those without (11.72 months). The ALBI, MELD and MELD-sarcopenia were associated with mortality. ALBI had AUROC of 0.717 (95% CI: 0.659 - 0.771), MELD had AUROC of 0.656 (95% CI: 0.595 - 0.713) and MELD-sarcopenia had AUROC of 0.798 (95% CI: 0.744 - 0.845). The ALBI and MELD scores had comparable AUROC (p=0.081). The MELD-sarcopenia had superior AUROC than MELD (p=0.001) and ALBI (p=0.05). CONCLUSION: MELD-sarcopenia is better prognostic model than the ALBI and MELD scores in HCC patients awaiting liver transplantation.
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Baseline Sarcopenia is Associated with Lack of Response to Therapy, Liver Decompensation and High Mortality in Hepatocellular Carcinoma Patients.

OBJECTIVE: hepatocellular carcinoma (HCC) is a dreadful complication of liver cirrhosis. Aim was to study the effect of sarcopenia on the survival in patients with HCC. METHODS: we included 262 patients and were followed up for 12 months. Sarcopenia was calculated by skeletal muscle index (SMI). Sarcopenia was defined by SMI ≤39 cm2/m2 for women and ≤50 cm2/m2 for men. RESULTS: patients with sarcopenia (n= 113, 43.1%) were older, mainly males, Child-Pugh class B and smokers. Patients with sarcopenia had lower survival than those without (10.09 vs. 11.72 months). Survival was also lower in Barcelona clinic liver cancer stage C than B and A (9.02 vs. 11.21 vs. 11.89 months). Age and sarcopenia were hazardous of mortality (p <0.05). There was statistically significant difference of serial SMI in patients without baseline sarcopenia unlike patients with baseline sarcopenia. On follow up patients with sarcopenia had higher incidence of ascites (45% vs. 20.4%), spontaneous bacterial peritonitis (21.7% vs. 11.6%), hepatic encephalopathy (28% vs. 11.5%) and bleeding (22.9% vs. 12.7%). Totally patients with sarcopenia had higher incidence of progressive HCC (39% vs. 25.5%). CONCLUSION: Sarcopenia is associated with lack of response to therapy, liver decompensation and higher mortality in hepatocellular carcinoma patients.
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Evaluation of liver biopsy in Egyptian HBeAg-negative chronic hepatitis B patients at initial presentation: implications for therapy.

OBJECTIVES: A subgroup of HBeAg-negative chronic hepatitis B (CHB) patients with alanine aminotransferase (ALT) and/or hepatitis B virus (HBV)-DNA levels below the cutoff values of international guidelines may have significant liver disease and miss the opportunity for early treatment. Histopathological changes of HBeAg-negative CHB patients at initial presentation irrespective of HBV-DNA and/or ALT levels to increase the likelihood of patients for treatment are evaluated. METHODS: CHB patients attending Cairo Liver Center from January 2006 to May 2008 had biochemical, serological, and virological screening as well as liver biopsy that was assessed by Metavir score. RESULTS: Fifty-two HBeAg-negative CHB patients (46 male and 6 female) with a median age of 37.5 years were included in the study. Significant fibrosis (>or=F2) was found in 26% (5/19) of patients with serum HBV-DNA <2,000 IU/ml, and 53% (21/40) of patients with ALT level <2xULN. Liver biopsy increased candidacy for treatment by nearly 25% before implementation of the recommended lower ALT levels (30 U/l for male and 19 U/l for female patients), and by 21.2% after implementation of the lower ALT level. Implementation of the lower ALT level increased the candidacy of patients for treatment by 4% (two patients), whereas liver biopsy increased eligibility for treatment by 55.8 % (27/49). CONCLUSIONS: Liver biopsy is more reliable than either ALT or HBV-DNA levels in the decision to treat Egyptian HBeAg-negative CHB patients, even with the implementation of the recommended lower ALT levels.

Interleukin-10 promoter polymorphisms in hepatitis C patients with and without Schistosoma mansoni co-infection.

BACKGROUND/AIM: Interleukin (IL-10) plays a major role in chronic hepatitis C virus (HCV) disease pathogenesis, in particular in Schistosoma mansoni (S. mansoni) co-infected patients. Given that interindividual variations in IL-10 production are influenced by functional polymorphisms in the IL-10 gene promoter, we determined the frequencies of common (-1082, -819 and -592) IL-10 promoter polymorphisms in chronic HCV patients with and without S. mansoni co-infection and healthy controls, and investigated their association with the degree of histological activity index (HAI) and response to interferon-ribavirin therapy. METHODS: Genomic DNA from 99 patients and 62 healthy controls, born in the same geographical hyperendemic area, was studied by the polymerase chain reaction, followed by restriction enzyme digestion. Sera were assessed for S. mansoni antibodies. RESULTS: The frequencies of IL-10 polymorphisms at positions -1082, -819 and -592 from the transcription start site were comparable between HCV patients and controls, as well as between HCV mono-infected and either S. mansoni co-infected patients or controls. The grade of inflammation and the stage of fibrosis showed no association with IL-10 polymorphisms. The frequencies of S. mansoni co-infection and IL-10 genotypes/haplotypes were insignificantly different between non-responders and responders to combination therapy. No effect of other factors like age, gender, HAI group scores and serum alanine aminotransferase and aspartate aminotransferase levels was observed on response to therapy in our patients. CONCLUSION: Our findings suggest that common IL-10 (-1082, -819 and -592) genotypes/haplotypes do not influence the degree of HAI and response to combination therapy or susceptibility to HCV infection with and without S. mansoni co-infection.

Hepatocellular carcinoma in Egypt: a single center study over a decade.

AIM: To identify the trend, possible risk factors and any pattern change of hepatocellular carcinoma (HCC) in Egypt over a decade. METHODS: All HCC patients attending Cairo Liver Center between January 1993 and December 2002, were enrolled in the study. Diagnosis of HCC was based on histopathological examination and/or detection of hepatic focal lesions by two imaging techniques plus alpha-fetoprotein level above 200 ng/mL. The duration of the study was divided into two periods of 5 years each; period I (1993-1997) and period II (1998-2002). Trend, demographic features of patients (age, gender, and residence), risk factors (HBsAg, HCV-Ab, schistosomiasis and others) and pattern of the focal lesions were compared between the two periods. Logistic regression model was fitted to calculate the adjusted odds ratios for the potential risk factors. The population attributable risk percentage was calculated to estimate the proportion of HCC attributed to hepatitis B and C viral infections. RESULTS: Over a decade, 1328 HCC patients out of 22,450 chronic liver disease (CLD) patients were diagnosed with an overall proportion of 5.9%. The annual proportion of HCC showed a significant rising trend from 4.0% in 1993 to 7.2% in 2002 (P = 0.000). A significant increase in male proportion from 82.5% to 87.6% (P = 0.009); M/F from 5:1 to 7:1 and a slight increase of the predominant age group (40-59 years) from 62.6% to 66.8% (P = 0.387) in periods I and II respectively, reflecting a shift to younger age group. In the bivariate analysis, HCC was significantly higher in rural residents, patients with history of schistosomiasis and/or blood transfusion. Yet, after adjustment, these variables did not have a significant risk for development of HCC. There was a significant decline of HBsAg from 38.6% to 20.5% (P = 0.000), and a slight increase of HCV-Ab from 85.6% to 87.9% in periods I and II respectively. HBV conferred a higher risk to develop HCC more than HCV in period I (OR 1.9 vs 1.6) and period II (OR 2.7 vs 2.0), but the relative contribution of HBV for development of HCC declined in period II compared to period I (PAR% 4.2%, 21.32%). At presentation, diagnostic alpha-fetoprotein level (> or = 200 ng/mL) was demonstrated in 15.6% vs 28.9% and small HCC (< or = 3 cm) represented 14.9% vs 22.7% (P = 0.0002) in periods I and II respectively. CONCLUSION: Over a decade, there was nearly a twofold increase of the proportion of HCC among CLD patients in Egypt with a significant decline of HBV and slight increase of HCV as risk factors. Alpha-fetoprotein played a limited role in diagnosis of HCC, compared to imaging techniques. Increased detection of small lesions at presentation reflects increased awareness of the condition.

Impact of cigarette smoking on response to interferon therapy in chronic hepatitis C Egyptian patients.

AIM: Smoking may affect adversely the response rate to interferon-alpha. Our objective was to verify this issue among chronic hepatitis C patients. METHODS: Over the year 1998, 138 chronic hepatitis C male Egyptian patients presenting to Cairo Liver Center, were divided on the basis of smoking habit into: group I which comprised 38 smoker patients (>30 cigarettes/d) and group II which included 84 non-smoker patients. Irregular and mild smokers (16 patients) were excluded. Non eligible patients for interferon-alpha therapy were excluded from the study and comprised 3/38 (normal ALT) in group I and 22/84 in group II (normal ALT, advanced cirrhosis and thrombocytopenia). Group I was randomly allocated into 2 sub-groups: group Ia comprised 18 patients who were subjected to therapeutic phlebotomy while sub-group Ib consisted of 17 patients who had no phlebotomy. In sub-group Ia, 3 patients with normal ALT after repeated phlebotomies were excluded from the study. Interferon-alpha 2b 3 MU/TIW was given for 6 mo to 15 patients in group Ia, 17 patients in group Ib and 62 patients in group II. Biochemical, virological end-of- treatment and sustained responses were evaluated. RESULTS: At the end of interferon-alpha treatment, ALT was normalized in 3/15 patients (20%) in group Ia and 2/17 patients (11.8%) in group Ib compared to 17/62 patients (27.4%) in group II (P = 0.1). Whereas 2/15 patients (13.3%) in group Ia. and 2/17 patients (11.8%) in group Ib lost viraemia compared to 13/62 patients (26%) in group II (P = 0.3). Six months later, ALT was persistently normal in 2/15 patients (13.3%) in group 1a and 1/17 patients (5.9%) in group Ib compared to 9/62 patients (14.5%) in group II (P = 0.47). Viraemia was eliminated in 1/15 patients (6.7%) in group Ia and 1/17 patients (5.9%) in group Ib compared to 7/62 patients (11.3%) in group II, but the results did not mount to statistical significance (P = 0.4). CONCLUSION: Smokers suffering from chronic hepatitis C tend to have a lower response rate to interferon-alpha compared to non-smokers. Therapeutic phlebotomy improves the response rate to interferon-alpha therapy among this group.

Effect of surveillance for hepatocellular carcinoma on tumor staging and treatment decisions in Egyptian patients.

PURPOSE: Egyptian hepatocellular carcinoma (HCC) patients present at advanced stages. We aimed to study the influence of surveillance versus non-surveillance on HCC staging and the potential therapeutic options. METHODS: A retrospective study to evaluate the effect of surveillance on early detection of HCC among cirrhotic patients from 2003 to 2008. Patients examined every 6 months using ultrasound and α-fetoprotein (α-FP) (group A) and those diagnosed with those that present for the first time symptomatically or incidentally (group B). Groups were compared for α-FP level, tumour characteristics, severity of liver disease; tumour staging was evaluated by Okuda, CLIP and BCLC staging systems, in addition to the potential therapeutic options. RESULTS: Group A comprised 122 HCC cases and group B 473. Surveillance improved HCC detection: at the stage of single nodule in 62.3% in group A versus 52.2% in group B, (P = 0.046) and reduced the percentage of HCC with portal vein thrombosis in 16.4 versus 33.8%, (P = 0.000) and the percentage of α-FP >400 ng/ml in 19.5 versus 32.6%, (P = 0.006) in groups A and B, respectively. Surveillance doubled the detection of HCC at early stage of BCLC (25.4 vs. 11.9% P = 0.000) and doubled the patients' chance for loco-regional ablation (12.3 vs. 5.9%, P = 0.015) and liver transplantation (10.7 vs. 3.2%, P = 0.001) in groups A and B, respectively. CONCLUSION: HCC surveillance increases early detection of HCC and doubled the chances for curative options. Implementation of both HCC surveillance and cadaveric liver transplantation programs should be recommended in Egypt.

Response of hepatitis C genotype-4 naïve patients to 24 weeks of Peg-interferon-alpha2b/ribavirin or induction-dose interferon-alpha2b/ribavirin/amantadine: a non-randomized controlled study.

BACKGROUND AND AIM: Currently, pegylated interferon is the most effective therapy for hepatitis C but its cost is out of reach of most patients in the developing countries. The aim of this study was to assess the response rate of genotype-4 patients to 24 wks of peg-interferon-alpha2b (Peg-IFN-alpha2b) and ribavirin (RBV) or interferon-alpha2b (IFN-alpha2b) with RBV and amantadine (AMD) as an alternative option. METHODS: In a controlled study, 180 biopsy-proven naïve chronic hepatitis C patients were allocated into three groups based on their financial affordability to any of the study regimens. Group I (control) comprised 40 patients who received Peg-IFN-alpha2b in a flat dose of 100 mug/wk (the dose available in Egypt) plus RBV 1,000-1,200 mg per day based on body weight for 48 wks. Group II comprised 70 patients who received the same regimen for 24 wks. Group III comprised 70 patients who received induction-dose triple therapy (IDTT) in the form of IFN-alpha2b 3 MU once daily for the first 4 wks then reduced to TIW for 20 wks plus RBV 1,000-1,200 mg per day based on body weight and AMD 100 mg twice daily for 24 wks. Six patients from group I, eight patients from group II, and four from group III discontinued the study either due to financial limitations and/or intolerable adverse effects of the drugs. RESULTS: Intention-to-treat analysis revealed that sustained virological response (SVR) achieved in 22 (55.0%), 34 (48.6%), and 20 (28.6%) in groups I, II, and III, respectively. Adherence-to-treatment analysis (80/80/80) revealed that SVR achieved in 22 (64.7%), 34 (54.8%), and 20 (30.3%) in groups I, II, and III, respectively. In absence of eradication of hepatitis-C-virus-RNA at week 12, there was virtually no chance of achieving SVR. These data collectively may indicate that genotype 4 is "not difficult to treat" as previously reported. CONCLUSION: Response of genotype-4 patients to 24 wks of Peg-IFN-alpha2b/RBV did not significantly differ from 48 wks, but was significantly higher than IDTT. Although SVR achieved by IDTT is less than Peg-IFN-alpha, yet it might provide a second option when the latter is not affordable. Early virological response should be used as a predictor to SVR to avoid unnecessary expenses in nonresponders patients.

Non-interferon-based therapy: an option for amelioration of necro-inflammation in hepatitis C patients who cannot afford interferon therapy.

OBJECTIVES: Interferon (IFN) therapy is not affordable by the majority of Egyptian patients. Our aim was to tailor an effective and inexpensive regimen that ameliorates hepatic necro-inflammatory activity among chronic hepatitis C (CHC) patients. METHODS: One hundred and seventy naïve CHC patients with elevated alanine aminotransferase (ALT) (>1.5-fold) and detectable hepatitis C virus (HCV)-RNA by polymerase chain reaction, who cannot afford IFN-based therapy were randomly allocated either to non-interferon-based therapy (N-IFN-BT) (group I) or silymarin therapy (group II). Group I comprised 87 patients (biopsy proved chronic hepatitis in 62 patients) who were administered a daily combination of ribavirin (600-800 mg) plus amantadine (200 mg) and ursodeoxycholic acid (UDCA) (500 mg) for 24 weeks. Group II comprised 83 patients who were administered Silymarin 450 mg/day for 24 weeks. RESULTS: Statistical evaluation was conducted on 82 patients from group I and 72 from group II because of the withdrawal of five and 11 patients from Groups I and II, respectively. Age, sex, social status and biochemical parameters were comparable in both groups. Normalization of ALT at the end of treatment was achieved in 58.5% and 15.3% (P<0.001), whereas end of treatment virologic response (ETVR) was achieved in 2.4% and 0% of Groups I and II, respectively. Twenty-four weeks after cessation of therapy, sustained biochemical response (SBR) was achieved in 28% and 2.8% (P<0.001), while sustained virologic response (SVR) was maintained in 2.4% and 0% of the patients in Groups I and II, respectively. In Group I, histopathological examination revealed a decreased activity index by an average score of 1.5 points among 38/62 of the rebiopsied patients. CONCLUSION: Twenty-four weeks N-IFN-BT achieved a fourfold-higher ETBR and a tenfold-higher SBR compared with silymarin therapy, which reflects an improvement of necroinflammatory activity as proven by repeat histopathology.