Esmat 2015.

Methods	Randomised clinical trial with parallel group design (2 groups).
Participants	101 participants (25% women) aged 18 to 60 years, mean age 40 years, with chronic HCV genotype 4. Inclusion criteria: aged 18 to 60 years, chronic HCV infection genotype 4 for > 6 months by detectable serum quantitative HCV‐RNA, naive to treatment, compensated liver disease with the following minimum haematological and biochemical criteria (haemoglobin ≥ 12 g/dL for men and ≥ 11 g/dL for women, WBC > 3500/mm3, granulocyte count > 1500/mm3, platelet count > 75,000/mm3, albumin and thyroid function tests within normal limit, and antinuclear antibody ≤ 1:80). US‐guided liver biopsy within 12 months prior to study entry, using a semiautomatic true‐cut needle (16G). Exclusion criteria: other liver diseases, decompensated liver cirrhosis, hepatocellular carcinoma, liver biopsy contraindication, unsuitable for combined IFN and ribavirin treatment due to persistent haematological abnormalities, receiving medications known to affect vitamin D3 level or metabolism (calcium, vitamin D supplementation, oestrogen, alendronate, isoniazid, thiazide diuretics, long‐term antacids, calcium channel blockers, cholestyramine, anticonvulsants, and orlistat), clinically evident osteomalacia (waddling gait, bone pain, and pathological fractures), renal diseases or parathyroid diseases, and BMI > 35.
Interventions	Intervention: vitamin D3 15,000 IU/week + PEG‐IFN‐α‐2b + ribavirin (n = 50). Control: placebo + PEG‐IFN‐α‐2b + ribavirin (n = 51). PEG‐IFN‐α‐2b (Peg‐Intron‐MSD) at 1.5 mg/kg subcutaneous injection once/week. Ribavirin (Rebetol, MSD) dose determined by body weight (< 75 kg = 1000 mg/day; ≥ 75 kg = 1200 mg/day in 2 separate oral doses after meals morning and night) for 48 weeks. Vitamin D3 given as oral solution with juice once weekly for 48 weeks.
Outcomes	Primary outcome: SVR. Secondary outcome: stage of hepatic fibrosis.
Stated aim of study	To assess role of vitamin D supplementation on response to treatment in people with chronic HCV 4 and its possible relation to stage of hepatic fibrosis.
Notes	Additional information received through personal communication with authors on 23 January 2017.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method of sequence generation not specified.
Allocation concealment (selection bias)	Low risk	Allocation sequence hidden in sequentially numbered, opaque, and sealed envelopes.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	No blinding, but we judged that outcomes were not likely to be influenced by lack of blinding.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	No blinding of outcome assessment, but we judged that outcome measurements were not likely to be influenced by lack of blinding.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Insufficient information to assess whether missing data in combination with the method used to handle missing data were likely to induce bias.
Selective reporting (reporting bias)	Unclear risk	Unclear whether all predefined and clinically relevant and reasonably expected outcomes reported.
For‐profit bias	Unclear risk	Trial may or may not have been free of for‐profit bias as trial did not provide any information on clinical trial support or sponsorship.
Other bias	Low risk	Trial appeared free of other factors that could put it at risk of bias.