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Introduction: Nonalcoholic Fatty Liver Disease (NAFLD) has become the leading cause of liver morbidity. The Mediterranean diet can improve NAFLD and may be offered as treatment. Intermittent fasting has been shown to improve aspects of the metabolic syndrome, but its effect on NAFLD is inconclusive., Objectives: A randomized - controlled study assessed the outcomes of the effect of the Mediterranean diet alone versus the Mediterranean diet in combination with intermittent fasting for 16 weeks in patients with NAFLD (1:2 ratio) and subsequent long term follow-up. Outcomes parameters included the response to treatment as measured by body mass index (height and weight), waist-hip ratio, and levels of steatosis and fibrosis as measured by transient elastography. In addition, satisfaction and compliance were assessed via questionnaires (ten-point Likert scale)., Results: Sixteen out of 40 recruited patients completed the study (69% men, mean age 45.8 ± 12.1 years, mean baseline BMI 33 ± 4.5), of which nine patients were included in the arm of diet in combination with intermittent fasting. The two groups were similar at baseline with regard to age, gender, height, weight, BMI, waist to hip ratio, and levels of steatosis and fibrosis. At the study end, a significant decrease was observed (p-value = 0.01) in the degree of steatosis from 316.4 ± 50.4 to 279 ± 35.7 DB/m. The improvement in steatosis was significant (p-value = 0.01) in the intermittent fasting group (an improvement of 13.8 ± 20.9%) as compared to the group without intermittent fasting (4.2 ± 20.9%, no statistical significance). The other physical outcome measures did not show a statistically significant change between values at the beginning of the study and study end (16 weeks). Participant questionnaires were completed at a mean follow-up of 1.6 ± 0.2 years and showed a high level (8.3 ± 1.69) of compliance at the beginning of the study in both groups. In addition, both study groups expressed a similar degree of difficulty in adhering to the assigned diet. By study end, participant adherence was significantly higher (p-value = 0.04) among the Mediterranean diet group alone (7 ± 2) as compared to the group in combination with intermittent fasting (4.9 ± 2). Furthermore, those in the Mediterranean diet alone group were more willing (9.7 ± 0.8) to continue the dietary treatment after completing the study as compared to the intermittent fasting group (6.4 ± 0.7) (p-value = 0.03). Study participants in both groups reported that their dietary treatment was overall beneficial (7.9 ± 2.2)., Conclusions: This study, given the limitations of a small sample size, suggests that a Mediterranean diet in combination with intermittent fasting improves steatosis in NAFLD patients over the long term as compared to Mediterranean diet without time restricted eating.

Introduction: Patients with hepatocellular carcinoma (HCC) receive Model for End-Stage Liver Disease (MELD) prioritization points. These aim to prevent waiting list drop-out due to tumor progression. This practice has resulted in an imbalance in the access of HCC vs. non-HCC patients to liver transplantation (LT). Recently this practice has been questioned and the policy in Israel changed, reducing the priority to "low risk" HCC patients., Aims: To analyze the survival on the waiting list of HCC patients and the influence of the change in our policy., Methods: This is a retrospective study analyzing the National Transplant Center data for HCC patients who were listed for LT from January 2009 to December 2018. Statistical analyses were performed to identify independent predictors of outcome. Outcomes of HCC patients were compared to non-HCC controls separately before (period A) and after implementation of changes in the allocation policy (period B)., Results: The study population consisted of 1188 patients listed for LT , 231 due to HCC .The transplant rates were 179/231 (80%) for the HCC group and 390/957 (40%) for cirrhotic patients and the drop-out rates 10.8% vs 31% respectively. During period B the transplantation rate for cirrhosis increased to 44% for cirrhotic and remained 77% for HCC. The outcome of "low risk" HCC with no priority on the waiting list, did not change significantly., Conclusions: HCC patients had higher chances to get transplanted and better survival compared to non-HCC patients. With the new policy the transplantation rate for non-HCC increased without deteriorating the HCC patient's outcome. HCC patients still have better survival on the list than non-HCC liver transplant candidates. Further analysis is needed to adjust HCC candidates' prioritization and improve organ allocation in Israel.

Ascites is the most common manifestation of decompensated liver cirrhosis. The life expectancy of cirrhotic patients developing uncomplicated ascites is 50% for 3 years. Refractory ascites, electrolyte imbalance, hepato-renal syndrome and spontaneous bacterial peritonitis may develop. Successful treatment can improve symptoms and outcomes. This article summarizes the Israeli Association for the Study of the Liver guidelines for diagnosis and management of cirrhotic ascites and its complications.

The current standard of care for the treatment of hepatitis C virus (HCV) is a combination of pegylated interferon alpha (PeglFN] -2a/2b and ribavirin for 24-48 weeks, according to the viral genotype. This treatment is associated with significant side effects and achieves sustained virologic response (SVR) in only 40%-50% of genotype 1 HCV-infected patients. The recent development of direct-acting antiviral agents (DAAs] targeting critical steps of the virus life-cycle led to a major breakthrough in the management of HCV infection. The DAAs include protease inhibitors and polymerase inhibitors. The recently approved protease inhibitors boceprevir and telaprevir, when given with PeglFN and ribavirin in HCV genotype 1 patients, result in a much higher SVR rate [70%] among treatment-naïve and treatment-experienced patients, compared with Peg-IFN and ribavirin. In specific groups of patients this enables a shorter duration of treatment. The DAA-containing regimens are approved for HCV genotype 1 infection in HCV treatment-naïve and HCV treatment-experienced including cirrhotic patients. The Israeli Ministry of Health has recently approved the use of boceprevir (Victretis) and telaprevir (Incivo) in combination with PeglFN and ribavirin for the current standard of care treatment of HCV genotype 1 patients. The consensus opinion of a panel of national HCV-experts appointed by the Israeli Association for the Study of the Liver is presented in this report. These Israeli consensus guidelines indicate the current best practice for the use of boceprevir and telaprevir in the management of genotype 1 chronic HCV infection.

Unlabelled: We evaluated the vertical transmission of hepatitis B virus (HBV) in the vaccine era after 1992., Methods: A cross-sectional descriptive study was conducted in the year 2005-2006 at Clalit Health Services, Jerusalem. Children at age > or = 1 year born after 1992, with HBsAg positive mothers, were evaluated., Results: A total of 22,683 HBsAg tests were performed for 20,415 patients (11,186 Jewish and 9,229 Arabs). The prevalence of positive HBsAg was 2.64% (95% CI, 2.43-2.87] among the general Jerusalem population. It was 3.9% among the Arab population (95% CI, 3.34-4.34), compared to 1.59% [95% CI, 1.37-1.84) among the Jewish population. Data from fertile women aged 18-44 years, showed a prevalence of HBV carrier state of 1.7% (total); 2.84% (95%CI, 2.43-3.3) in Arab women as compared to 0.66% [95% CI, 0.48-0.9) among Jewish women. Of 164 Arab positive HBsAg women, we identified 157 mothers for 409 children at age > or = 1 year born after 1992. Data for 188 children of 70 mothers was collected. The prevalence of vertical infection among the child cohort (positive anti-HBc) as well as the prevalence of chronic infection [positive HBsAg) were 8.4% (95% CI, 4.71-13.1) and 4.4% (95% CI, 1.8-7.6], respectively; 37.1% of these children had negative anti-HBs titters, compared to 41.4% with antiHBs 11-100 mlU/ml and only 21.5% with titters above antiHBs 100 mLU/mL; 48% (23/48) children received passive-active vaccine combination; 35% (17/48) children received only active vaccination; 12.5% (6/48) were born to mothers prior to HBV infection diagnosis and received only the active vaccine; 4.5% (2/48) received no vaccination at all., Conclusion: HBV vertical transmission is highly prevalent in our tested Arab cohort, in spite of the universal vaccination program, suggesting its failure. Improvement of physician awareness and double vaccination of infants of carrier mothers will likely reduce the vertical transmission.

Direct hyperbilirubinemia, may result from a variety of pathologies, including structural obstructions with biliary tract occlusions (as in cholelithiasis), infections (e.g. hepatitis) and genetic disorders (Rotor's and Dubin-Johnson's syndrome). One of the less common and probably more frequently underdiagnosed causes is benign recurrent intrahepatic cholestasis (BRIC). First described in 1959, BRIC was further classified into two subgroups which differ in their pathogenesis and clinical manifestation. Both BRIC types originate from impaired function bile salt excretion from hepatocytes to the canaliculi which is mediated by the bile salt export pump (BSEP) which is located on the hepatyocyte membrane, unevenly distributed within the membrane lipid bilayer. In BRIC type-I, a mutation impairs the asymmetrical distribution of BSEP. In BRIC type-II, a mutation occurs directly damaging the BSEP. Apart from cholestasis, clinical manifestations of BRIC type-I include extra-hepatic symptoms such as watery diarrhea, pancreatitis and hearing impairment. Patients with BRIC type-II present mainly with hepatobiliary disease such as colelithiasis. In the past, BRIC was conventionally considered to result in no more than canalicular cholestasis, however several reports have associated BRIC with fibrosis and porto-portal septa formation. Disease course may last between weeks and months, more common in females, at any age, and usually resolves spontaneously, although chronic liver disease has also been described. Treatment modalities range from expectant management, medication (cholestyramine, ursolit) or even surgery (biliary bypass/liver transplantation). This report describes a patient with BRIC type-II and reviews the relevant literature.

Background: For medical students studying in a traditional medical curriculum, advancement from the pre-clinical years to clinical clerkships requires a conceptual move from disease-oriented thinking to problem-oriented medicine., Objective: To implement an educational tool in the introductory course of clinical medicine that will assist students in the development of comprehensive medical reasoning, including the generation of a dynamic problem list, its assessment and the construction of investigative and treatment plans., Methods: Since 2001 a novel brief Problem-Based Learning (PBL) experience has been offered as a component of the Introduction to Medicine course given to 4th year medical students prior to the start of their clinical years at the Hebrew University Medical School. The brief experience consists of daily meetings given to small groups of students at the final stages of the pre-clinical courses. Each PBL day covers a single clinical case revealed sequentially over 3-5 structured sessions, interspersed with periods of self-directed learning. Cases are highly structured and contain all of the required information pertaining to the clinical problems presented., Results: Evaluations of this course over 4 years by both students and teachers have been outstanding, with students consistently stating in their written comments that the PBL experience was one of the most meaningful learning experiences they have encountered during the pre-clinical phase of their training., Conclusions: This brief PBL experience appears to help in building up the students' clinical competence during their first clerkship experiences. It may be especially useful for medical schools using the traditional medical curriculum.

Background: Standard anticoagulatn therapy for lower extremity DVT does not distinguish between proximal and distal veins. Catheter directed thrombolytic therapy is a new emerging aggressive option for suitable patients with proximal DVT., Objectives: Review of the literature and presentation of two patients in whom the procedure was successfully performed., Patients and Methods: Two patients with lower extremity DVT involving the iliac and femoral veins were treated with catheter directed urokinase infusion in addition to conventional anticoagulant therapy. In both cases underlying venous stenoses were identified and treated by balloon angioplasty and insertion of metallic stents. Thrombolytic therapy was continued for 36-60 hours at a rate of 100,000 units per hour., Results: Significant clinical and radiological improvement was obtained in both patients with restoration of centripetal venous flow in the deep venous system. No significant complication occurred. A persistent clinical benefit was seen at follow-up of 8 and 24 months respectively., Conclusions: Catheter directed thrombolytic therapy should be considered as adjuvant therapy for patients with acute proximal lower extremity DVT, in whom there are no contraindications. Underlying venous stenoses should be dilated and stented if necessary. Early restoration of venous flow results in rapid clinical improvement and may prevent the future development of post thrombotic syndrome.

Neurologic complications are very common following liver transplantation and appear in 30%-90% of the patients. These complications represent a wide array of etiologies, often presenting complicated diagnostic options. The primary liver disease for which the patient underwent the transplantation can cause neurologic complications, or they can be a presentation of a metabolic or vascular derangement. The medications given to liver transplanted patients can cause neurologic complication either directly via drug side effects or indirectly via immune-suppression and secondary opportunistic infections of the nervous system. We present two cases of liver transplanted patients, one suffering from a complex neurologic syndrome attributed to her primary Wilsons disease and the second with recurrent encephalopathy following transplantation attributed to a porto-systemic shunt. We review the current literature on the subject.

Guillain-Barre and other neurologic syndromes rarely occur as complications of viral hepatitis (A, B and C). Other neurologic syndromes have also been reported in serologically defined viral hepatitis, including mononeuritis, auditory neuritis, and seizures. Chronic hepatitis B and mononeuritis multiplex are found together in 31-54% of patients with periarteritis nodosa. The mechanisms of these associations are unknown, but may include direct cytotoxicity of the virus or immune-mediated damage. Vasculitis of the vasa nervorum plays an intermediate role, at least in some cases. We describe a 36-year-old man with acute non A-G hepatitis complicated by Guillain-Barre syndrome. The neurological manifestation resolved completely without specific therapy within 6 days, as the hepatitis resolved.